Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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insulin like growth factor 1 receptor(IGF1R) insulin like growth factor 1 receptor(IGF1R) Related Genes Homo sapiens
CYTOBAND 15q26.3,
GENERIF_SUMMARY X ray structure and autoregulation of the insulin-like growth factor 1 receptor kinase, Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling., Functional insulin-like growth factor-1/insulin-like growth factor-1 receptor-mediated circuit in human and murine thymic epithelial cells., cDNA probes were used to analyze the gene expression of IGF-I receptor in luteinized granulosa cells from different-sized follicles after ovarian hyperstimulation., results suggest that activation promotes neuroblastoma cell proliferation by regulating trans-membrane amino acid transport, results suggest a pathway of cancer cell adaptation to the tumor microenvironment in which conditions of the environment may induce expression of IGF1R, and this subsequent overexpression of the receptor may increase cell survival in such conditions, Autocrine production of IGF-I and IGF-II may via IGF-IR play a significant role in the growth and megakaryocytic differentiation of K562 cells., Insulin-IGF1 hybrid receptors have different tissue-specific responses based on their isoforms, The x-ray structure of the unactivated kinase domain of insulin-like growth factor-1 receptor (IGFRK-0P) is reported here at 2.7 A resolution., expression at normal levels in Nijmegen breakage syndrome cells, affects angiogenesis, growth, and metastasis of colon cancer, WT1-p53 interactions in gene regulation, IGF-1 receptor undergoes serine autophosphorylation and binds to 14-3-3, IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice, IGF-IR-mediated radioresistant signaling mechanism progresses through redundant downstream pathways, This receptor signals the inhibitor of apoptosis ASK1., signaling pathways mediated by insulin-like growth factor-I receptor are required for proliferation, invasion, and VPF/VEGF expression in a pancreatic carcinoma cell line, IGF-IR and IGF-IIR antisense genes could significantly restrain the malignant behavior of human hepatoma cells and might be useful in investigating a potential route for hepatocellular carcinoma gene therapy., First demonstration of insulin-like growth factor-I receptor on human ocular surface., Shrinkage in uterine volume induced by GnRH analogs seems to be related to reduction in IGF-I-R levels. IGF-I/IGF-I-R system might affect leiomyoma growth. Action of GnRH analogs on uterine leiomyomas might be related to the effects on IGF-I-R expression., Ribonucleoprotein complex assembly on the 5'-untranslated region of the IGF-IR transcript., Down- and up-regulation suggests that restoration of IGF-1R would be the result of receptor recycling and de novo synthesis and highlights its importance for T lymphocyte proliferation., Overexpressed and activated IGF1-R may increase the degree of transformation and motility of colon cancer cells by activating c-Src., Mdm2 physically associates with IGF-1R and that Mdm2 causes IGF-1R ubiquitination in an in vitro assay. Mdm2 serves as a ligase in ubiquitination of the IGF-1R and thereby causes its degradation by the proteasome system., human longevity are coregulated by an overlapping set of genes, contributing to the hypothesis that the impact of the IGF-I/insulin pathway on longevity is a property that has been evolutionarily conserved throughout the animal kingdom., Ligand activation of IGF-1R protects normal human mesangial cells from glycol-oxidant-induced apoptosis program. IGF-1R-activated ERK signaling phosphorylates Ser112 of mitochondrial Bad protein, linking IGF-1R with mitochondrial survival., IGF binding to the IGF1R initiates an intracellular signaling cascade in breast neoplasms that leads to changes in gene expression and cell biology [review], In IGF-IR dominant negative cells decrease in constitutive and inducible phosphorylation of IGF-IR and Erk1/2. Nuclear hypoxia-inducible factor-1alpha and secreted VEGF protein levels also significantly lower., IGF-1 receptor activation inhibits oxidized LDL-induced cytochrome C release and apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway., results suggest a novel function for the IGF-IR/IRS-1 pathway that involves regulation of the intracellular trafficking of Rad51 to the site of damaged DNA-a crucial step in the process of DNA repair by homologous recombination, results suggest a novel regulatory role of the C-terminus of IGF-IR in mediating cellular radioresistance that may be independent of survival signals transmitted through this receptor, role of IGF1 in cardiac myocytes in the absence of secondary effects, and downstream signaling pathways and transcriptional regulatory effects of the IGF1 receptor, To further understand the role of the type I insulin-like growth factor (IGF) receptor (IGF1R) in cancer metastasis we inhibited signaling via IGF1R using a C-terminal-truncated IGF1R., role of IGF-1R and c-Src in human pancreatic carcinogenesis. Coexpression of both these molecules may play important role in transformation of pancreatic ductal cells., The IGF1-R/Akt/Bcl-x(L) pathway may contribute to a more aggressive malignant phenotype, in a subset of colorectal cancers., These findings suggest that 14-3-3 proteins interact with the IGFIR in vivo and that this interaction may play a role in a transformation pathway signaled by the IGFIR., Coexpression of insulin receptor-related receptor and insulin-like growth factor 1 receptor correlates with enhanced apoptosis and dedifferentiation in human neuroblastomas., IGF I receptor is involved in apoptosis protection in human preadipocytes and adipocytes., IGF-IR mediated attenuation of antineoplastic agent-induced growth inhibition is dependent on IGF-I-induced PI3K signaling rather than IGF-I-induced MAPK signaling, Activation of IGF-I receptor can selectively enhance the previously reported IGF-I receptor pro-apoptotic signaling pathways., Transcription of the IGF-IR gene is under inhibitory control by a number of transcription factors with tumor suppressor activity, including BRCA1 and p53., Expression in breast cancer correlates with estrogen receptors alpha ansd beta., IGF-IR was expressed in primary breasttumors as well as in lymph node metastases, but the expression in primary tumors was more frequent, Single chain humanized antibody treatment down-regulated IGF-IR which appears to contribute to breast tumor growth inhibition., Ability of a monoclonal antibody to down-regulate the receptor may be an important antibody property in targeting the insulin-like growth factor-I receptor for the treatment of certain cancers., Human micro- and macrovascular endothelial cells express more IGF-IR than insulin receptor., PI3K/Akt and Raf/MEK/ERK pathways are intimately involved in IGF-1R-mediated cell cycle progression and prevention of apoptosis in hematopoietic cells, Compounds with inhibitory effects on IGF-1R may be useful in development of anticancer agents., overexpressing PTEN demonstrated that PC3 cells synthesize significantly lower levels of the IGF-IR precursor, IGFBP-3 inhibits IGF-I-mediated IGF type 1 receptor (IGF-IR) phosphorylation in 3t3 cells overexpessing human IGF1R, Shc and IGF-1R serve as key elements in the translocation of ERalpha to the cell membrane and in the facilitation of ERalpha-mediated rapid E2 action, muscarinic receptors may inhibit insulin signalling by promoting IRS-1 tyrosine dephosphorylation and/or by uncoupling IRS-1 from the stimulated IGF-1 receptor by stimulating IRS-1 serine phosphorylation, Data show that differentiated thyroid cancers of children and adolescents express IGF-I and IGF-I receptors., All squamous cell carcinomas and basal cell carcinomas were negative for IGF-IR expression. Six of seven Merkel cell carcinomas stained with IGF-IR strongly, showing cell membrane accentuation and a perinuclear dot-like pattern., Activation of IGF-1R by the chimeras reflected their binding affinities whereas the phosphorylation of the two insulin receptor isoforms was more complex., an interrelationship is now known to exist between the IGF and EGF receptors [review], DICE1 has a growth-suppressing activity and interferes with anchorage-independent growth of IGF-IR transformed tumor cells dependent upon IGF-I signaling, Increases in IGF-IR decrease beta1 integrin expression, and enhance cell migration in neuroblastoma cells., The cyclolignan PPP efficiently inhibits phosphorylation of IGF-1R without interfering with insulin receptor activity., The present data suggests that the IGF-IR gene is a novel downstream target in an ATM-mediated DNA damage response pathway., Data report that antagonism of the type 1 insulin-like growth factor receptor in combination with inhibitors of the epidermal growth factor receptor synergistically sensitizes human malignant glioma cells to CD95L-induced apoptosis., hyaluronan production is induced by GD-IgG in fibroblasts suggests that the IGF-I receptor and its activating antibodies may represent a key pathway through which important pathogenic events in thyroid-associated ophthalmopathy are mediated., IGF-I signaling may have a role in altered fetal growth and development, IGF-I receptor signaling and function in breast cancer is modulated by estrogen receptor alpha, Low levels of insulin-like growth factor type 1 receptor expression at cancer cell membrane is associated with liver metastasis in colorectal cancers, association between IGF-IR expression in the primary oral tumours and their stage, IGF-1R and the IGF system may have roles in progression of highly malignant soft tissue sarcoma, Data show that ionizing radiation causes stress-induced activation of insulin-like growth factor-1 receptor-Src-Mek-Erk-Egr-1 signaling that regulates the clusterin pro-survival cascade., The IGF-1 Receptor genes has been inactivated by homologous gene targeting., OxLDL downregulates IGF-1R via redox-sensitive pathways that are distinct from OxLDL signaling through MAPK- and PPARgamma-involved pathways but may involve a CD36-dependent mechanism, IGF-1 receptor was found in seminal plasma from fertile and infertile men, but no IGF-1 receptor was observed in sperm from patients with a history of more failed fertilization, IGF-IR level was lower in gastrinomas of patients who were rendered disease free and increased levels correlated with tumor growth, aggressiveness, extent, and with liver metastases., beta-arrestin has a role in ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase, The function of the ELAV RNA-stability factor HuR as a 5'-UTR-binding protein and dual-purpose translation repressor may be critical for the precise regulation of IGF-IR expression., CD221 is aberrantly expressed on human myeloma cells. Higher levels of CD221 are observed in patients & human myeloma cell lines with the most aggressive 14q32 translocations. CD221 expression has a negative prognostic impact in MM patients., leptin and the IGF system of IGF-I, IGFBP-2, and IGF-I receptor do not interact directly in a cell culture model of neuroepithelioma cells, In sedentary, clinically stable maintenance hemodialysis patients as compared to sedentary normal individuals, the mRNA levels for IGF-IEa, IGF-II, and the IGF-I receptor are decreased in vastus lateralis muscle, Data suggest that IGF-IR may be involved in the growth of a subset of craniopharyngiomas and points to the possibility of the involvement of IGF-IR inhibitors as a treatment modality., high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer, Existence of unidirectional IGF-IR/EGFR cross-talk mechanism whereby IGF-II, acting through IGF-IR, regulates basal and ligand-activated EGFR signaling and cell proliferation in a c-SRC-dependent manner in tamoxifen-resistant breast cancer., We found that the colon cancer cell lines Caco2, HT29, SW837, and SW480 express high levels of the IGF-1R receptor, and that both SW837 and SW480 cells display constitutive activation of this receptor., interplay between WT1 and ERalpha in control of IGF-IR gene transcription, Segregation of IGF-IR in and out of lipid rafts may dynamically regulate the pro- and anti-apoptotic effects of IGF-I on apoptosis induced by TNF superfamily members., CXCR4 is trans activated by IGF1R in human breast cancer epithelial cells, the IGF-IR gene is a novel downstream target for p63/p73 action, overexpression of IGF-IR exists in hematopoietic cells in myelodysplastic syndrome and acute myeloid leukemia marrows, which appears to contribute to disease progress, Our results do not support the hypothesis that the carrier state of IGF-IR G(+3174)A polymorphism has an impact on the risk of ROP in infants., Serum starvation significantly increases PDGFbeta-R but not IGF-1-R mRNA & protein expression in smooth muscle cells. Distribution of PDGFbeta-Rs & IGF-1-Rs in atherosclerotic lesions may indicate an effect of serum starvation on SMCs in arterial wall., Breast cancer MCF-10A cells over-expressing the IGFIR formed large, misshapen acinar structures with filled lumina and disrupted apico-basal polarization., demonstrate significant overexpression of the IGF-IR in human pheochromocytomas, selected examples of tumor suppressors, including BRCA1, p53, and WT1, whose mechanism of action involves regulation of IGF-IR gene expression. [REVIEW], PQ401 inhibits autophosphorylation ofIGF-IR in cultured human breast cancer cells with an IC50 of 12 micromol/L and phosphorylation of the isolated kinase domain of the IGF-IR., Weaker placental IGF-1R staining in the placentae of diabetic pregnancies associated with septal hypertrophic cardiomyopathy suggests reduced expression of IGF-1R, Tyr-1135 plays an important role in stabilizing the autoinhibited conformation of the activation loop, while Tyr-1136 plays the key role in stabilizing the open, activated conformation of IGF1R within the tyrosine kinase catalytic domain., The up-regulation of IGF-IR expression in hepatocytes of patients with CHC could constitute an attempt to stimulate hepatocyte regeneration., IGF-1 receptor kinase is inhibited by hydrogen peroxide, IGF1R overexpression might activate pERK1/2 and pAKT in hormone receptor-positive breast cancer, but activate only pAKT in hormone receptor-negative breast cancer., Data show that hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant., both IGF1R and the TGF-beta /BMP pathway could play important roles in immune function in sickle cell anemia and their polymorphisms may help identify a "bacteremia-prone" phenotype, IGF-IR and c-Met cooperate to induce migration and invasion of human pancreatic carcinoma cells., Differential expression of insulin receptor, IGF-IR, and IGF-I in adhesion fibroblasts may contribute to pathogenesis of fibrosis in diabetic patients., These data suggest that IGF-1R and PKCdelta are required to stimulate PKB phosphorylation in response to BMOV in HepG2 cells., Precise orientation of IGF-I within the IGF-I-IGF-1R complex involving the IGF-I C-domain binding to the IGF-1R CR domain., transcriptional activation of the IGF-IR gene by Cav-1 requires an intact p53 signaling pathway, Pharmacological intervention against IGF-IR with simultaneous activation of GSK3beta could be highly effective against medulloblastomas, polymorphisms in the IGF-1R and IGFBP3 genes, but not IGF-1 or IGFALS, may be associated with altered survival among subgroups of breast cancer patients defined by menopausal status, Luteolin inhibits IGF-1R/AKT signaling, these results provideing a new insight into the mechanisms that luteolin inhibits testicular cancer cells., the expression of IGF-I and IGFIR genes may undergo substantial change over the course of breast tumorigenesis, and the pattern of changes may be associated with breast cancer prognosis, These results demonstrate that IGF1R is downregulated by P53, and that siRNA targeting of IGF1R increases liver cancer cells sensitivity to adriamycin and promotes apoptosis., Data provide evidence that an increase in IGFIR gene copy number results in aberrant expression in the blastemal compartment of some Wilms' tumors and is associated with an adverse outcome in these patients., Small interferin RNA downregulates this protein and inhibits growth of a breast cancer cell line in vitro and in nude mice., An amino-acid-substitution mutation is postulated to be the cause of intrauterine and postnatal growth retardation in a family., small interfering RNA for IGF-1R significantly inhibited the formation of lung metastases in nude mice., Overexpression of a constitutively activated IGF-IR (CD8-IGF-IR) was sufficient to cause transformation of immortalized human mammary epithelial cells and growth in immunocompromised mice., EGFR depletion induced enhancement of IGF1R ubiquitylation and degradation., EGFR cannot compensate for IGF1R depletion., Intense insulin-like growth factor-1 receptor is associated with local and metastatic prostate cancer, IGF-related peptides are most likely synthesized locally and might be involved in the initiation and/or progression of neointimal thickening of primary arteriovenous fistulas., The IGF-I/IGF-I-receptor pathway plays an essential role in the development and maintenance of the malignant phenotype by favoring cell survival & inhibiting apoptosis. Review., Common SNP (GAA1013-->GAG) in the IGF1R gene may be associated with premature pubarche in children., VHL inactivation leads to IGF1R upregulation, contributing to renal tumorigenesis and potentially also to chemoresistance., This study suggests that the IGF-IR is a substrate for gamma-secretase and may mediate a function independent of its role as a receptor tyrosine kinase., E2 can activate a linear pathway involving the sequential activation of IGF-IR, MMP, HB-EGF, EGFR, and MAPK in MCF-7 breast cancer cells, the two systems, TRs and IGF1/IGF1R could be functionally associated., Dual targeting of IGF-1R and PDGFR increased cell death in both glioma 18 and glioma 38 cell lines in comparison to inhibition of either receptor alone. In addition, co-inhibition of IGF-1R and PDGFR increased radiosensitivity in 18 cells., The juxtamembrane region of IGF1R plays an important role in limiting the basal activity of the receptor., that endogenous IGF-1 and IGF-2 receptors can independently initiate ERK1/2 signaling and point to a potential physiologic role for IGF-2 receptors in the cellular response to IGF-2, Insulin-like growth factor-I receptor mediates the prosurvival effect of fibronectin., Overexpression and dimerization with EGF receptor produces a therapeutic targeet in head and neck cancer xenografts., Different members of Rho GTPase family regulate IGF-II-mediated EVT cell migration differentially, depending upon whether it signals through IGF1R or in an IGF1R-independent manner., evidence for the expression of IGF-1R in nerve sheath tumors in NF1, Data show that aldosterone increases elastin production via a mineralocorticoid receptor-independent pathway involving insulin-like growth factor-I receptor signaling., Inhibition of IGF1R using a blocking antibody or lentivirus-delivered shRNA reduced hESC self-renewal and promoted differentiation, Data suggests that the IGF-IR gene is a physiologically relevant downstream target for BRCA1 action., Upregulation of IGF-1 receptor expression is associated with oral cancer., The apoptosis of DNA-damage-induced p53 is reduced in Igf-1r(-/-) mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism, IGF-I receptor and beta1-integrin signaling may play an important role in protective effect of hyaluronic acid on interleukin-1-induced inhibition of collagen biosynthesis in cultured human chondrocytes., curcumin and FOLFOX work through attenuation of the EGFR and IGF-1R signaling pathways, Identification of epitopes of insulin-like growth factor-I receptor recognized by monoclonal antibodies., Blocking Hsp90 disrupts IGF-I and IL-6-induced proangiogenic signaling cascades by targeting IGF-IR and STAT3 in pancreatic cancer, The results do not support the association of the most prevalent insulin-like growth factor I receptor gene polymorphism and the risk of advanced retinopathy of prematurity., UVB irradiation leads to an activated p38 MAPK that is regulated in an IGF-1R-dependent manner, leading to NF-kappaB p50, PC furin is a major IGF-1 receptor convertase., Altered osteoblast proliferation in human osteoporosis may result from dysregulation of IGF-I receptor signaling, including constitutive activation of the IRS-2/Erk signaling pathway., Signal transduction pathways underlying the enhanced cell migration reveal that the IGF-I-IGFBP-VN complex stimulates a transient activation of the ERK/MAPK signaling pathway and a sustained activation of the phosphatidylinositide 3-kinase/AKT pathway., IGF-I receptor gene G3174A polymorphism is associated with lumbar spine BMD in postmenopausal Korean women, TRAIL may play an important role in atherosclerosis by regulating IGF1R expression in VSMC in an NF-kappaB-dependent manner., MT1-MMP localization and IGF-1R expression in prostate carcinoma could be predictive biomarkers for aggressive disease., one mechanism of keratinocyte resistance to UVB-induced carcinogenesis involves the induction of IGF-1R-dependent premature senescence, simultaneous inhibition of both Focal adhesion kinase and the insulin-like growth factor-I receptor represents a potential novel therapeutic approach in human pancreatic adenocarcinoma, In conclusion, SS18-SSX and IGF-1R seem to play important but different roles in maintaining malignant growth of synovial sarcoma cells., Sequence analysis of the IGF1 and IGF1R genes of female centenarians showed overrepresentation of heterozygous mutations in the IGF1R gene among centenarians that are associated with high serum IGFI levels and reduced activity of the IGFIR, induction of decorin expression in angiogenic, as opposed to quiescent, endothelial cells promotes a motile phenotype in an interstitial collagen I-rich environment by both signaling through IGF-IR and influencing alpha2beta1 integrin activity, downregulation of type I IGF receptor expression is associated with breast cancer., A critical role for IGF-IR signaling in prostate tumorigenesis with an important IGF-IR-dependent growth control mechanism., dysregulation of the IGF-IR internal ribosomal entry site through changes in the activities of RNA-binding translation-regulatory proteins could be responsible for IGF-IR overexpression in a proportion of human breast tumors., Akt and its downstream targets FoxO3a and GSK3 regulate a survival pathway in VSMCs and that their deregulation due to a reduction of IGF1R signaling may promote apoptosis in atherosclerosis., A genetic variation at the IGF1R gene locus is associated with spinal disc degeneration, in line with involvement of IGF1R in cartilage metabolism., The G-A polymorphism in the IGF-1R gene may affect the susceptibility to brain ischemia in the Chinese population., IGF-IR-positive expression, performance status 1 or 2, and diffuse type tumors were significant predictors of poor survival in gastric cancer., The data suggest that phosphoenolpyruvate -dependent decrease of collagen biosynthesis in cultured human skin fibroblasts may undergo through depression of alpha(2)beta(1) integrin and IGF-IR signaling., ER alpha is involved in activation of ERK/mitogen activated protein kinase by genistein by its early association with IGF-IR, leading to hyper-responsiveness of leiomyoma cells, confirming that ER signaling is enhanced by activation of ERK/MAPK., IGF-IR appears to be a critical determinant of response to numerous cancer therapies.[REVIEW], Suppression of IGF1R gene expression by shRNA enhances the chemosensitivity of A549 cells to DDP both in vitro and in vivo., Activation of IGF-II/IGF-IR signaling is likely a progression switch selected by function that promotes tumor cell dissemination and aggressive tumor behavior., Common IGF1 and IGF1R gene polymorphisms, such as single nucleotide polymorphisms and variable number of tandem repeats, have been investigated with conflicting results with respect to small for gestational age-related outcomes.[review], In this crystal structure, the IGF1RK active site is occupied by Tyr1135 from the activation loop of an symmetry (two-fold)-related molecule, allowing visualization of the initial trans-phosphorylation event in the activation loop of an RTK., MVP and IGF-1R expression were related in clinical cervical tumours and confer reduced long-term local control in patients who achieved clinical complete response to radiochemotherapy., Inhibition of the IGF-IR pathway and aromatase is synergistic in two independent estrogen-dependent in vitro models of breast cancer, Competitive equilibrium binding assays revealed significantly reduced specific binding to the insulin, IGF-I, and IGF-II and their receptors in both the anterior cingulate and vermis of alcoholic human brains., c-Cbl is a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis, Higher IGF-I Receptor is associated with venous invasion and liver metastasis in colorectal cancer., Local recurrences of invasive breast carcinoma were associated with high-grade tumors, PR-negative and low active-IGF1R, IR and IGF-IR are present in human preadipocytes and adipocytes. Differentiation is characterized by an increased IR/IGF-IR ratio., Microvascular endothelial cells are sensitive to IGF-I but resistant to insulin due to a preponderance of IGF-I receptors and sequestration of insulin receptors into insulin/IGF-I hybrid receptors., The role of the IGF/insulin receptors in cervical cancer cell lines with different Human papillomavirus (HPV) status, SiHa (HPV positive), and C33a (HPV negative), was assessed., The ubiquitin ligase Nedd4 mediates oxidized low-density lipoprotein-induced downregulation of insulin-like growth factor-1 receptor., Data provide an immunohistochemical evaluation of insulin-like growth factor I receptor status in cervical cancer specimens., Insulin-like grow factor 1 receptor associates with thyroid-stimulating hormone receptor in situ; together they may comprise a functional antigenic complex in thyroid and orbital tissue., IGF-1 receptor signaling alterations could explain thyroid-associated ophthalmopathy [review], The divergent signaling functions of IGF1R and EGFR suggested the potential for synergism by a combination of therapy directed at the two receptors., In lymphocytes from patients with GD, IGF-1 enhanced IgG production (p < 0.05) and increased B cell expansion (p < 0.02) in vitro while those from control donors failed to respond, Report overexpression of IGF1R in pancreatic islets of nesidioblastosis patients., The epithelial expression of IGF1R is elevated in mildly active UC., Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells., FAK, mTOR and IGF-IR are inhibited by TAE226 in esophageal cancer cells, Anti-IGF-1R strategies may offer a useful approach in molecular therapy for colorectal cancer, which has the potential to improve outcomes., Val(43), Phe(28), and Val(14) (equivalent to site 1) are critical to IGF-1R and IR binding, whereas mutation to alanine of Gln(18) affects only IGF-1R and not IR, High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients., Over-expression of IGF-1R is related to poor differentiation of nasopharyngeal carcinoma., pIGF-IR is upregulated in a majority of follicular thyroid carcinomas., Regulatory role of IRS-2 on the expression of IGF-IR through PKCdelta in pancreatic cancer cells., Our findings suggest that more frequent IGF-IR(+) T cells in graves' disease cannot be attributed to genetic determinants, Results shows the preferential IGF-1R immunolocalizatrion in specific areas of the developing embryo, suggesting a role of IGF1-R for the optimal maturation of those areas, during developing human embryos., Treating ovarian cancer with cisplatin showed that enhanced IGF-IR expression and autocrine IGF-I are associated with hyperactivation of the IGF-IR and phosphatidylinositol-3-OH kinase (PI3K) pathways in cisplatin-resistant cells., Data show that the expression of IGF-IR was positively related with the expression of COX-2 and PCNA., Increased numbers of IGF-1R-positive cells were found in nasal polyps compared to nasal mucosa in the epithelium & stroma, suggesting involvement of innate immunity in nasal polyp formation., Data show that IGF-IR resistant to miR145 is not down-regulated by miR145 but fails to rescue colon cancer cells from growth inhibition, and indicate that down-regulation of IRS-1 plays a significant role in the tumor suppressor activity of miR145., enhanced IGF-1 signaling inhibits glucose-induced apoptosis in HUVECs by reducing mitochondrial dysfunction, and maintaining the mitochondrial retention of cytochrome-c., identified novel reciprocal functional interactions between IGF-IR and NPM-ALK, A polymorphic variant of the insulin-like growth factor 1 receptor (rs2229765, a minor allele) is found to correlate with male longevity in an Italian population., Findings suggest that increased IGF-I signaling may also be involved in processes leading to retinal vascular pathology in humans., Hassall's corpuscles are involved in the local regulation of T-cell development and thymus plasticity during aging by IGF-I/IGF-IR-mediated cell signaling pathway., Data suggest that the expression of IGF-1R or VEGF may be related to the development, invasion and metastasis of gastric carcinoma., Data validate IGF1R as a therapeutic target in CC-RCC, and support the evaluation of IGF1R-inhibitory drugs in patients with renal cancer., A strong positive correlation between insulin as well as IGF1 receptor and AdipoR1, but not AdipoR2, expression could be observed., these data suggest a role for FAK in phosphorylation, signaling and stability of the IGF-1R., the direct binding to IGF-1 to integrin alphavbeta3 plays a role in IGF-1 signaling through ternary complex formation (alphavbeta3-IGF-IGF1R), findings suggest that G1013A most likely modulates IGF-IR function, possibly by influencing gene transcription or mRNA stability, and represents a plausible mechanistic link underlying the association between obesity and esophageal malignancy, FAK-NT2 (a.a. 127-243) domain directly interacts with the N-terminal part of the IGF-1R intracellular domain., This study indicates that downregulation of IGF-IR results in significant inhibition of tumor growth in vitro., over-expression of IGF1R is associated with Gastrointestinal Stromal Tumors., The common IGF-IR gene polymorphism G1013A modulates the risk of obesity for esophageal adenocarcinoma., E2F1 expression induced a significant increment in endogenous IGF-IR levels. ChIP assays showed enhanced E2F1-binding to the IGF-IR promoter in E2F1-expressing cells., results indicate that the levels of placental insulin-like growth factor 2 and insulin-like growth factor I receptor may be involved in the development of macrosomia, The expression of factor IGF-II and its receptor, IGF-1R was significantly higher in breast carcinoma having Loss of Heterozygosity at WT1 locus., Two single nucleotide polymorphisms of the IGF-1 receptor gene are related to left ventricular hypertrophy in patients with essential hypertension., Overexpression of IGF1R is associated with squamous cell carcinoma in non-small-cell lung cancer patients., In NSCLC cell lines, high levels of total IGF-1R are associated with moderate sensitivity to R1507 (IGF-1R antibody), insulin action on platelet function in platelets expressing hybrid Insulin/IGF-1 receptors, Taken together, these findings suggest that the structural movements within the receptor upon ligand binding are small and are possibly limited to local rotation of domains., Data show that disruption of IGF1R rendered cells more susceptible to anoikis., Study we provide evidence of an association between the age-related decline in IGF-I with the progressive decrease in bone formation markers in premenopausal women., Results show that IGF-IR can inhibit PKC-alpha gene transcription and thereby block the synthesis of PMA-regulated MMPs, suggesting that within the same cells, IGF-IR can act as both a positive and negative regulator of MMP expression and function., Results reveal a link between the IGF-I pathway in PCCs and CCL5 pathway in MSCs through the interaction of those cells., findings show that sequence variation in IGF1R may influence insulin secretory function, Studies provide further evidence for a role of the IGF-1R in skin, and imply that reduced expression of IGF-1 in geriatric skin could be an important component in the development of aging-related non-melanoma skin cancer., Studies show that BMS-754807 is a reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor and increases poly ADP ribose polymerase and Caspase 3 cleavage., findings indicate that TNF-alpha induces a loss of sensitivity to stimulation by IGF-I, through reducing amount of IGF-I/insulin hybrid receptor and the stimulation of HR tyrosine kinase activity by IGF-I., A statistically significant correlation was demonstrated between IGF-IR expression and Fuhrman nuclear grading and survival in patients with renal cell carcinoma. However, it seems that IGF-IR cannot be considered as an independent prognostic factor., Uveal melanomas express HGF, c-Met, EGFR, and IGF-1R, These results suggest that IGFR-1 expression may be useful as a prognostic marker in patients with small-cell lung cancer -extensive disease., PRL diminished IGF-I-induced IGF-IR internalization, which may result from reduced SHP-2 association with IGF-IR, because we demonstrated an essential role for SHP-2 in IGF-IR internalization, Results suggest that trastuzumab resistance in breast cancer might be overcome by therapeutic strategies that jointly target erbB3, erbB2, and IGF-IR., a novel heterozygous IGF1R mutation identified in a girl with short stature and six relatives was evaluated. results in a kinase-deficient IGF1R, which is likely to cause the phenotype of intrauterine and postnatal growth retardation., Anti-IGF-IR antibodies with different epitope-specificities can cause downregulation and internalization of IGF-IR from clathrin-coated pits., overexpression for IGF-1R is associated with adenocarcinoma of the esophagus., Activation of IGFR occurs at least in part via SirT1-mediated repression of PTP1B, there is a SUMOylation-mediated mechanism of IGF-1R signaling that has potential implications for gene regulation, Notch-1 stimulates survival of lung adenocarcinoma cells during hypoxia by activating the IGF-1R pathway., Data show that 5-benzylidenethiazolidine-2,4-dione and 5-(furan-2-ylmethylene)thiazolidine-2,4-dione were identified as potent and selective IGF-1R inhibitors., study suggests for the first time a putative role of IGF1R variants in individual susceptibility to metabolic syndrome-related phenotypes, in particular on the risk of having insulin resistance and arterial hypertension, The IGF-1R gene is neither associated with the occurrence nor the curve severity of adolescent idiopathic scoliosis., IGF-IR expression in primary breast cancer is an independent favorable prognostic factor., pathological dysregulation of IGF1R translational control may contribute to development and progression of breast cancer, and breast metastasis in particular, IGF1R and IGF2R differential expression may contribute to the increased risk of malignant transformation in young african american (AA) women and to the more aggressive breast cancer phenotype observed among AA breast cancer patients., In non-small cell lung carcinoma IGF1R protein and gene expression does not associate with survival, whereas high IGF1R gene copy number harbors positive prognostic value., A novel amino acid substitution in the IGF1R gene resulted in intrauterine and postnatal growth retardation of an affected patient, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction, higher IGF-I and IGF-IR contents observed in small for gestational age placentas and the lower contents observed in large for gestational age placentas compared with adequate for gestational age placentas may be influencing human fetal growth., Data describe the role of the IGF-IR in bladder cancer and show that it required the activation of the Akt and MAPK pathways as well as IGF-I-induced Akt- and MAPK-dependent phosphorylation of paxillin., Insulin-like growth factor-I receptor has a role in proliferation and motility of pancreatic cancer, Disruption of IGF-1R signaling increases TRAIL-induced apoptosis, Results suggest that prostate cancer progression is associated with a decrease in insulin-like growth factor-I receptor (IGF-IR) expression that could be the result of impaired ability of androgen receptors to stimulate IGF-IR gene expression., Overexpression of IGF-IR and PKC may play an important role in the carcinogenesis and development of laryngeal squamous cell carcinoma., Two functionally distinct allelic forms of the IGR1R Loop3 poly(U)-tract are prevalent in the human population, and it is conceivable that germ-line or somatic variations in this sequence could predispose individuals to development of malignancy, Resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and activation of p53., IGF-IR might be taken as a marker of clone cells in myelodysplastic syndromes, IGF-1R has a role in primary and metastatic undifferentiated carcinoma of the head and neck, hybrid insulin/IGF-I receptor (hybrid-R), which is present in endometrial carcinoma cells, may have an important role in mediating IGF- and insulin-induced cell growth and in preventing apoptosis., Studies indicate that inhibiting the IGF-1R signaling pathways early in the carcinogenic process results in reduced cell proliferation and survival, leading to decreased tumor formation., The reciprocal regulation of gamma-synuclein and IGF-I receptor expression creates a circuit that modulates IGF-I signaling., Randomized, phase II study of the insulin-like growth factor-1 receptor inhibitor IMC-A12, with or without cetuximab, in patients with cetuximab- or panitumumab-refractory metastatic colorectal cancer., Data demonstrate a cross-talk between IGF-1R and AT-1R in AT-II and IGF-1-induced Cx43 expression in SV SMCs involving Erk 1/2 and downstream activation of the AP-1 transcription factor., High expression of IGF-1R is associated with thymic malignancies., Rhabdomyosarcoma pathogenesis involves increased IGF1R expression that enhances AKT and Bcl-x(L)-mediated cell survival., Results demonstrated that miR-7 regulates the IGF1R/Akt signalling pathway by post-transcriptional regulation of IGF1R., SPCA1 inhibites the processing of IGF1R in MDA-MB-231 cells., (111)In-R1507 and (89)Zr-R1507 are new tracers to noninvasively determine IGF-1R expression in vivo in breast cancer xenografts using SPECT and PET., Data indicate that RACK1 serves as a direct mediator between loss of pVHL function and enhanced IGF-IR signaling pathway in RCC., P. acnes can induce the formation of comedones by stimulating the IGF/IGF-1R system, insulin-like growth factor-1 receptor is a binding partner of Loop 6/TIMP, RNA interference against IGF-IR successfully inhibited the expression of IGFIR in human OVCAR3 ovarian cancer cells., The heterozygous mutation described in this study reduced IGF1R expression and represents haploinsufficiency of the IGF1R gene. this mutation leads to abnormalities in the function of IGF1R and also retards intrauterine and subsequent growth., Report significant up-regulation of Rap1 and IGF-IR in carcinoma in situ progressing to invasive breast cancers., Data show that Delta40p53 controls the switch from pluripotent ESCs to differentiated somatic cells by controlling the activity of full-length p53 at critical targets such as Nanog and the IGF-1 receptor., In the present study, we observed associations between the IGF-1/1R pathway, susceptibility to IgAN, and the pathologic progression of childhood IgA nephropathy., Increased IGF1R mRNA implies poorer patient prognosis among different breast cancer subtypes, Dopamine acting through its D(2) receptor, inhibits IGF-I-induced proliferation of gastric adenocarcinoma cells by up-regulating KLF4, a negative regulator of the cell cycle through down regulation of IGF-IR and AKT phosphorylation., The excessive activation of the IGF-1R signaling pathway is probably one of the mechanisms that caused resistance of 5-8F/Erbitux cells to cetuximab., Stable IgG-like bispecific antibodies directed toward the type I insulin-like growth factor receptor demonstrate enhanced ligand blockade and anti-tumor activity., small cell lung cancer is characterized by frequent high-IGF1R protein expression, increased gene copy number, and occasional occurrence of true gene amplification., Studies indicate that insulin, IGF-1, TrkA, and TrkC receptors as trophic and as dependence receptors., In this study they compared nIGF-1R accumulation in neoplastic and normal cells in relation to expression of IGF-1R and Ubc9., Findings suggest that Cav-1 and PTRF/Cavin could represent two relevant and distinct targets to modulate IGF-IR function., The IGF-IR expression is related to tumor size and T stage in lung adenocarcinoma, while there is no relation between IGF-IR expression and prognosis., Studies provide a clear biological rationale to test anti-IGF-IR/InsR therapy in combination with chemotherapy in patients with TNBC., IGF1R expression patterns in epithelial cells of benign breast biopsies were associated with an increased risk of subsequent breast cancer, IGF1R mutations may contribute to the risk and in some cases cause single suture craniosynostosis., IGF-1R activation represents a previously unrecognized key pathway involved in the mechanisms by which NT and NTR1 modulate colonic inflammation and inflammatory bowel disease., overexpressed in estrogen receptor-positive breast carcinomas, In genetic association studies, no association was found between the IGF-I receptor polymorphisms investigated and endometriosis in a Korean population of women., These findings indicate that IL-6 signaling cooperates with IGF-IR signaling in the prostate microenvironment to promote prostate tumorigenesis and progression to aggressiveness, intensity of anti-IGF-1R immunostaining for 21 patients with small-cell lung cancer was correlated to survival., Synchronized up-regulation of the insulinlike growth factor I receptor axis in tumor cells and intratumoral and adjacent arterioles could represent a mechanism of hepatocarcinogenesis and progression., these findings support the identification of the novel susceptibility gene IGF1R for predisposition by the fetal genome to being born preterm., P-cadherin cooperates with insulin-like growth factor-1 receptor to promote metastatic signaling of gonadotropin-releasing hormone in ovarian cancer via p120 catenin., IGF-IR is up-regulated and frequently activated in mantle cell lymphoma., Data suggest that FAK is critically involved in osteolytic metastasis and activated in tumors, pre-osteoclasts, mature osteoclasts, and bone stromal cells, and the FAK/IGF-1R inhibitor TAE226 may be used for cancer induced bone metastasis., A-IGF1R/Asp-IRS2/Val-UCP2 allele combination is associated with a decreased all-cause mortality risk and with an increased chance of longevity., Data show a novel protumorigenic mechanism in TEMs, Hsp90-capacitated overexpression of IGF-1R, which confers apoptosis evasion in malignant thymic epithelial cells., The human longevity-associated IGF type-1 receptor (IGF1R) variants are reduced-function mutations, implying that dampening of IGF1 signaling may be a longevity mechanism in humans., Data show that EI-04 as a superior cancer therapeutic in treating EGFR and IGF-1R pathway responsive tumors., research has found evidence that IGF1R mutations are causally linked to the aetiology of small for gestational age (SGA) [review], Data show that the 17-mer PNA formed a PNA(2), in breast cancer cells, IGF-2 activates ER-alpha and ER-beta, and modulates their translocation to nucleus, membrane organelles and mitochondria; IGF-2 actions are mediated by the IGF-1R and the insulin receptor, Data suggest that lentivirus-mediated shRNA targeting IGF-1R has the potential to develop as a clinical treatment method in advanced and chemoresistant endometrial carcinoma., IGF1R expression and activity via osteoprotegerin can modulate vascular smooth muscle cell calcification., Data indicate that the IGF receptors IGF1R showed significantly increased mRNA levels in alveolar and embryonal rhabdomyosarcoma compared to the normal skeletal muscle., Insulin-like growth factor-I receptor (IGF-IR) targeting with monoclonal antibody cixutumumab (IMC-A12) inhibits IGF-I action in endometrial cancer cells, Data show that HLE-B3 cells express only the IGF-1Ea and IGF-1R transcripts., insulin and IGF-I activate their cognate receptors and IGF-I also activates naturally occuring IGF-I/insulin hybrid receptors (HR) IGF-II activates insulin receptor, IGF-I receptor and HR, Inhibition of PI3K reduced rhTRAIL sensitivity independently of the cell line preference for either DR4- or DR5-mediated apoptosis signaling., hCSCs expressing only IGF-1R synthesize both IGF-1 and IGF-2, which are potent modulators of stem cell replication, commitment to the myocyte lineage, and myocyte differentiation, IGF-1R correlates with good prognostic markers among patients with early breast cancer and is differentially expressed with variable prognostic impact among breast cancer subtypes., Our data provide evidence that the IGF-1/IGF-1R signaling axis may play a causal role in antiestrogen resistance of breast cancer cells, despite continuous suppression of ER transcriptional function by antiestrogens., IGF1R internalization and co-localization with clathrin and CAV1 upon ligand binding, as well as the status of the IGF1R pathway, cellular proliferation, and the apoptosis of interfered and inhibited Ewing's sarcoma, were analyzed., Propose a Systems Biology approach to understand the molecular biology of EGFR and IGF1R pathways in non-small cell lung cancer., Fine details of insulin-like growth factor 1 receptor activation, inhibition, and asymmetry determined by associated hydrogen /deuterium-exchange and peptide mass mapping, Results suggest that IGF-1-IGF-1R autocrine pathway in melanoma is a possible target for therapy in human melanomas., Autoimmunity against IGF-1R is not specific for Graves' disease but may contribute to ongoing immune reactions., Data suggest that the relatively high expression of the IGF receptors in triple-negative breast cancer cells suggests that the IGF signal pathway may be important in controlling cell proliferation and cell survival in this subtype of breast cancer., Functional experiments showed that LL-37-dependent activation of the IGF-1 receptor signaling resulted in increased migratory and invasive potential of malignant cells., miR-99a is one of the regulators of the IGF-1R signaling pathway in keratinocytes, The IGF-IR and MAPK kinase pathway involving proteins ERK1/2 showed more significant phosphorylation in the 1,595 cells compared to the observed in the MCF-7 cell line., IGF-1R can be considered a biomarker for the stage and risk of carcinogenesis during neoplastic initiation and progression along the colorectal normal mucosa-polyp-cancer sequence, IGF1R overexpression is associated with resistance to cetuximab in metastatic colorectal cancer., the present study demonstrated that expression of IGF1R was lower in moderately to poorly differentiated lung adenocarcinoma, and that low IGF1R expression was associated with poor prognosis in patients with lung adenocarcinoma., IGF1R mRNA expression appeared to be a good prognostic marker both in the entire cohort and in the luminal subtype group., After IGF-I stimulation, CTK is recruited to IGF-IR and its recruitment facilitates CTK's subsequent association with phospho-SHPS-1., IGF1R is a Notch1 target, and Notch1 signaling is required to maintain IGF1R expression at high levels in T-ALL cells., association between a novel IGF1R nonsense mutation and a variable degree of alterations in prenatal and postnatal growth and in carbohydrate metabolism., decorin loss may contribute to increased IGF-IR activity in the progression of bladder cancer, In muscle, the most notable changes were 28% lower gene expression of IGF-1Ea and 40% lower expression of IGF-1Ec in the postmenopausal non-users than in premenopausal women, and 28% higher expression of IGF1-receptor in HRT users than in non-users., We genotyped single-nucleotide polymorphisms of IGF1, IGF2, IGF1R, IGF2R, IGFBP1, IGFBP3, IGFBP5, IRS1, IRS2, and IRS in pancreatic cancer patients, Metformin disrupts erbB2/IGF-1R complexes, erbB3 and IGF-1R expression and activity., IGF-1R is an independent prognostic marker for osteosarcoma patients and increased expression of this molecular is correlated with metastasis of osteosarcoma., While IGF-1R was significantly correlated to colorectal tumor size & depth of invasion in univariate analysis, only tumor size had a strong association in multivariate analysis., Knockdown of InsR and/or insulin-like growth factor-I receptor inhibited growth of 3 of 4 long-term estrogen-deprived MCF-7 cell lines., histone deacetylase inhibitor vorinostat interacts with the insulin-like growth factor signaling pathway, erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines, Data show that Rac1 was highly activated in PTEN deficient and IGF-IR overexpressing Trastuzumab-resistant cells in a HER2-independent manner., Zyflamend inhibited Insulin-Like Growth Factor I stimulated cell growth, IGF Type 1 Receptor, and androgen receptor expression and its nuclear localization in CWR22Rv1 cells., The gefitinib treated cells displayed increased levels of phosphorylation in IGF-1R., effect of mutations in IGF1 and IGF-1R genes are explained in terms of effect on ligand binding and receptor activation; severity of patient phenotype can generally be correlated to the effect of the mutation on protein structure and function [review], Polyubiquitination of insulin-like growth factor I receptor (IGF-IR) activation loop promotes antibody-induced receptor internalization and down-regulation., activating mutation of PIK3CA, loss of PTEN, or IGF1R expression have a role in round cell transformation, the mammary tumors that develop in MTB-IGFIR transgenic mice, p53 regulates IGF-IR gene expression in uterine serous carcinoma cells via a mechanism that involves repression of the IGF-IR promoter, Data show that that the IGF1R pathway is a potential therapeutic target for patients with malignant peripheral nerve sheath tumor (MPNST)., IGF-IR might identify a subset of biliary tract carcinomas with a particularly aggressive phenotype and is a candidate therapeutic target in this disease., These data suggest a role of IGF1R on the risk for advanced age-related macular degeneration in this group of subjects., For the IGF-1R rs2229765 polymorphism, as male carriers of the homozygous A/A genotype survived longer, while the IL-6 rs1800795 genotype did not influence overall or sex-specific longevity., Results suggest that EGR-1 may stimulate prostate cancer cell growth through up-regulation of IGF-1R and indicate that down-regulation of EGR-1 could be an effective therapeutic approach against prostate cancer., Data show that inhibitors of Stat3, IGF-IR and Rho GTPase were the most promising therapeutic agents for ovarian cancer., IGF-IR stimulated IGF-IR gene expression, IR inhibited IGF-IR promoter activity., The p.E121K/E234K variant is the cause of intrauterine growth retardation and the most severe postnatal growth failure described to date in a patient with IGF1R defects., High IGF1R is associated with postoperative recurrence in patients with adenocarcinoma in non-small-cell lung cancer., This study has therefore lead to a greater understanding of the mechanisms of IGF-II binding and activation of the IGF-1R and IR-A., examined the differential role of the IGF system in esophageal adenocarcinoma and squamous-cell carcinoma and its association with visceral obesity; results indicate IGF-1 axis has a key role in progression of esophageal cancer and represents a plausible mechanism through which visceral obesity impacts on esophageal adenocarcinoma risk and tumor biology, Data support the concept for dual IGF-1R/IR targeting in hepatocellular carcinoma (HCC)., The allele A at rs1976667 SNP of IGF-IR gene is a risk factor for idiopathic short stature (ISS)., NKX3.1 inhibits IGF-1R expression and its signalling pathway in human prostatic carcinoma PC3 cells., Data suggest that tumor-derived IGF-2 in the microenvironment maintains angiogenesis in the presence of IGF-1R-targeted antibodies allowing tumor progression., our findings define an IGF-IR-mediated mechanism of cancer cell survival that is critical for metastatic colonization of the liver., As many patients present with few altered clinical and laboratory data, IGF1R defects must be suspected in cases of small for gestational age without postnatal growth recuperation., short interfering RNA (siRNAs) for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice, This study demonistrated that IGF-1 receptor beta subunit (IGF-1Rbeta) was significantly increased in skeletal muscel in patient with amyotrophic lateral sclerosis., nuclear IGF1R associates with the transcription factor LEF1 and increases promoter activity of LEF1 downstream target genes cyclin D1 and axin2., study of hypothesis that IGF-IR overexpression may be involved in MRP-2 mediated multidrug resistance in colorectal cancer cells; findings improve current understanding of the biology of IGF-IR and multidrug resistance, High IGF-1R expression was associated with squamous cell carcinoma than adenocarcinoma in non-small-cell lung cancer., Overexpression of IGF-1R might play an important role in the formation of nasal polyps. IgE-mediated hypersensitivity has no contribution to the overexpression of IGF-1R., The results of this study suggest a novel link between a mutation at the IGF-IR L2 domain and intrauterine and postnatal growth retardation., The overexpression of IGF-1R is colerated with lymph node metastasis, differentiation and clinical stage of esophageal squamous cell carcinoma. Down-regulation of IGF-1R can inhibit the proliferation of esophageal cancer EC9706 cells in vitro., Abnormal IGF-IR and VEGF-C expression may be important in lymph node metastasis of endometrial adenocarcinoma and might be used to evaluate the prognosis., IGF-1R+1013(G/A) polymorphism alone or in combination with IGF-2R +1619(G/A) polymorphism was associated with the overall survival period in patients with advanced NSCLC after treatment with platin-based chemotherapy., IGF-IR expression level on the clone cells from the myelodysplastic syndrome cases was markedly elevated compared to the corresponding level on normal cells., c-Met, epidermal growth factor receptor, and insulin-like growth factor-1 receptor are important for growth in uveal melanoma and independently contribute to migration and metastatic potential, discuss some of the recent results on the functional role and potential clinical use of the IGF-1R, one of the major mediators of growth and survival for multiple myeloma, Patients whose chordomas show a moderate to strong staining intensity in >/= 50% of tumour cells for IGF-1R (36%) might benefit most from IGF-1R targeting., probe enables us first to lock the GABA(B) receptor in an inactive state and then activate it with a positive allosteric modulator, thereby permitting monitoring of the dynamic of the protein complex associated with IGF-1R transactivation, we confirmed that novel shorter soluble IGF-IR 223/STOP and 325/STOP possessed almost the same antitumor effects as reported for 486/STOP., Inactivation of TROP2 due to loss of heterozygosity or by DNA methylation may play an important role in lung cancer tumourigenicity through losing its suppressive effect on IGF-1R signalling and tumour growth., miR-223 contributes to IGF1R regulation, but may act in concert with other genes and/or microRNAs to alter T-cell acute lymphoblastic leukemia biology., an absence of N-linked glycosylation at N913 led to a lack of membranous localization of IGF1R and figitumumab insensitivity, Epigenetic regulation of PITX2 during the course of the disease may lead to orchestrated control of the AR and IGF signaling pathways., This requires active ADAM17, a membrane associated metalloproteinase, and the phosphorylation of IGF-1R., Ganitumab, a fully human anti-type-1 insulin-like growth factor receptor antibody, was well tolerated and demonstrated antitumor activity in patients with advanced recurrent Ewing family tumors or desmoplastic small round cell tumors., GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting beta-arrestin 1 association., Insulin promotes the proliferation of Reh cells. High expression levels of IR and IGF-IR may be closely related with the growth of leukemia cells., Succinate dehydrogenase-deficient gastro-intestinal stromal tumors are characterized by IGF1R overexpression., genetic association studies in a population of German children, MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor., Patients who had high baseline IGF-1 levels had significantly higher disease control rate (DCR) than patients who had low baseline IGF-1 levels ., Data suggest that IGF-1R shRNA delivery can be valuable for RNA interference therapy to tumors in vivo., IGF-1 receptor activation triggers an increase in p75 neurotrophin receptor protein expression in hippocampus., Nuclear localisation of IGF-1R is an easily testable biomarker associated with a better progression-free survival and overall survival for patients treated with IGF-1R Ab therapy., SFYYS motif controls the organization of the IGF-1R C terminus relative to the kinase domain. Its phosphorylation by GSK-3beta restrains kinase activity and regulates receptor trafficking and signaling., strong protein expression of IGF-1R and EGFR was observed in thymic carcinoma and in both thymoma and thymic carcinoma, respectively. However,IGF-1R or EGFR gene amplification was rare in thymic epithelial tumors irrespective of protein expression., these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in colorectal cancer cells that contributes to malignancy of colorectal cancer., A novel heterozygous IGF1R missense mutation in exon 7 was identified in a short-statured girl with severe prenatal growth retardation and microcephaly; the same mutation was identified in her mother and grandmother., PI3K activity bound to IGF-IR, which is continuously sustained by IGF-I stimulation, is required for IGF-I-induced cell proliferation., IGF-IR expression positively correlates with PTEN and inversely correlates with NRP2 in prostate tumors, Human cardiac microvascular endothelial cells express more IGF1Rs than IRs, and mainly react to IGF1 due to the predominance of IGF1Rs and insulin/IGF1 hybrid receptors., study demonistrated that the first time that zinc can induce IGF-1Rbeta protein degradation in neurons via NEDD4-mediated ubiquitination and the subsequent UPS mechanism., The nuclear localization and function of the IGF-1R/INSR (Hybrid-R) and the role of IGF-1/IGF-1R and Hybrid-R signaling in the human corneal epithelium., The consistent lack of IGF1R expression in intestinal gastrointestinal stromal tumors should be considered an additional immunohistochemical marker in the differential diagnosis between them and non-gastrointestinal stromal tumor sarcomas., Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth., IGF1R may be a risk factor of susceptibility in PTC., MVP and IGF-1R expression are related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease, IGF-1R plays a role in the development of uveal melanoma, which may be induced by activation of the PI3K/AKT pathway., miR-148a and miR-152 act as tumor suppressors by targeting IGF-IR and IRS1, and that restoration of miR-148a/152 expression may provide a strategy for therapeutic application to treat BC patients., Rare IGF1R variants exerting a moderate effect on stature are present in the general population., The identification of an inactivating IGF1R mutation in the present cohort should encourage further studies of larger series to establish the precise frequency of this molecular defect in children with growth impairment of a prenatal onset., Results demonstrate that miR-122 functions as a tumor suppressor and plays an important role in inhibiting the tumorigenesis through targeting IGF1., horizontal transfer of the mRNA for IGF-1R to tubular cells through exosomes potentiates tubular cell sensitivity to locally produced IGF-1 providing a new mechanism underlying the powerful renoprotection of few Bone marrow-mesenchymal stem cells., IGF1R activation partially reverses cell cycle arrest caused by gefitinib in OSCC cells. IGF1R stimulation does not eliminate the gefitinib-induced increase in total p27, phosphorylation state and subcellular localization are altered., Data indicate that SDHB-deficiency was tightly associated with overexpression of IGF1R protein and transcript, and Biallelic inactivation of the SDHA gene was identified in 5 of 11 SDHB-negative gastrointestinal stromal tumors., Insulin-like growth factor 1 triggers a fast and independent nuclear calcium (Ca2+) signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes., Cathepsin X deficiency leads to a reduced phosphorylation of the IGF-I receptor in response to IGF-I stimulation., Studies indicate that insulin receptor (IR) and IGF Type 1 Receptor (IGFR) have been identified as important partners of Grb10/14 and SH2B1/B2 adaptors., conclude that inhibition of IGF-1 receptor tyrosine kinase activity by PQIP suppresses breast cancer-induced bone turnover and osteolysis, a model whereby IGFBP7 binds to unoccupied IGF1R and suppresses downstream signaling, thereby inhibiting protein synthesis, cell growth, and survival., IGF1R overexpression in KIT/PDGFRA WT GIST could be driven by the loss-of-function of the SDH mitochondrial complex., IGF-1R is highly expressed in lung squamous cell carcinoma and mucinous adenocarcinoma, although copy number alterations in the IGF-1R gene were rare., IGF-1R mRNA expression was also significantly higher in Follicular adenoma, nodular goiters, and Papillary thyroid carcinoma compared with the controls., Patients with concomitant IGF1R/EGFR fluorescence in situ hybridization immunohistochemistry had a worse disease-free survival and overall survival, IGF1R coupled with Sdc1 is required for activation of the alphaVbeta3 integrin and for VEGFR2 signalling., 2-fold, P < .001), possibly attributable to sequestration of IGF-I., With locally advanced pancreatic cancer, SNP rs1124736 (IGF1R) was associated with improved survival if they had a copy of the G allele., IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer., The regulation of IGF1 receptor expression by microRNA-100 in metatstatic and nonmetastatic pancreatic tumor cell lines is reported., The constitutive gene expressions of estrogen receptor beta and SDC-4 are mediated mainly through the EGFR signaling axis, whereas SDC-2 expression is regulated by both EGFR and IGFR pathways., the LRP6(R611C) mutation diminishes TCF7L2-dependent transcription of the IR while it increases the stability of IGFR and enhances mTORC1 activity., Neutralization of IGF1R signaling enhances the cytotoxic effects of antineoplastic agents in endometrial cancer., Although the exact roles of Cav-1 and IGF-IR in human cancer continue to be a matter of some debate, there is a strong evidence for an association between Cav-1 and IGF-IR in cancer development.[review], NF-kappaB bound the putative IGF1R promoter at position -230 to -219 bp., Data indicate statistically significant correlations were observed between the number of circulating epithelial tumor cell (CETC) and IGF-IR and VEGFR-2 expression., MiR-181b overexpression inhibited cell proliferation, migration, invasion, and tumorigenesis by targeting IGF-1R and its downstream signaling pathways., Small interfering RNA-mediated IGF-1R knockdown could mimic the effect of enforced miR-497 expression on the malignant phenotypes of cervical cancer cells, Our results indicate that GRK2 has contrasting roles on HepG2 cell growth by negatively regulating the IGF-1R signaling pathway and cyclins' expression., Small, intragenic deletions of IGF1R in two unrelated families affected primarily with neuropsychiatric phenotypes including developmental delay, intellectual disability and aggressive/autoaggressive behaviors, are reported., Results strongly suggest that IGF-1R is associated with malignancy in familial pheo/pgl and that IGF-1R expression in the primary tumour might be a useful tool to detect those patients harbouring pheo/pgl who have an increased risk of metastasis, the role of miR-16 as a tumor suppressor by targeting IGF1R in OS, Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC, IGF-1-induced delayed MET activation occurs in cell lines which express both receptors, suggesting that IGF-1R-mediated MET activation may contribute to tumorigenic properties of multiple cancer types when both growth factor receptors are expressed., IGF1R is differentially-expressed in different types of human sarcomas, and targeted blockade of IGF1R pathway may inhibit human OS migration through down-regulation of MMP-2/-9 expression, Data indicate that IGF-1R and SGLT1 interact in HEK293 and MCF7 cells, and IGF-1R siRNA transfection results in down-regulation of SGLT1., show that IGF-IR-mediated POU5F1 expression to form a complex with beta-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of lung adenocarcinoma stem-like cells, In theca cells and granulosa cells, insulin-like growth factor receptor-1 signaling is decreased in response to IGF-1 induced steroid production., Igf-1r SNP was found to be significantly associated with age at diagnosis of breast cancer in Jewish Ashkenazi BRCA1 mutation carriers., We report that miR-383 was downregulated in gliomas and inversely correlated with glioma pathological grades; we demonstrated that IGF1R expression is critical for miR-383 downregulation-induced cell invasion., data indicate that knocking down insulin-like growth factor-1 receptor (IGF-1R) expression through shRNA can render gefitinib-resistant cell lines sensitive., Our data support the notion that IGF-1R is a marker of stemness, and IGF-1R and its downstream PI3K/Akt/mTOR pathway are attractive targets for therapy directed against breast cancer stem/progenitors., (111)In-F(ab')-R1507 fragments can successfully target IGF-1R in Ewing sarcoma., Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R., IGF1 and IGF1R expression is associated with favorable clinicopathologic parameters and may involve early carcinogenesis of small intestinal neoplasms., 1) IGF1 induces signals under anchorage-independent conditions and that 2) R36E/R37E acts as a dominant-negative inhibitor of IGF1R (IGF1 decoy). Our results are consistent with a model in which ternary complex formation is critical for IGF signaling., Estradiol and IGF-I induced the rapid association of ER to IGF-IR., The existence of an autocrine loop in the IGF-1R/Akt pathway., The glycosylation of IGF-1R is necessary for the full activation of the receptor in response to androgen treatment and that perturbing this process can break the feedback loop between AR and IGF-1R activation in prostate cells., dual mutation of Tyr644 and Tyr664 in NPM-ALK abrogates its physical association with IGF-IR., Data suggest that detection of ductal carcinoma in situ (DCIS) based on marker expression during breast conserving surgery should be possible with a panel of molecular imaging tracers targeting CD44v6, GLUT1, HER2, IGF1-R, and EGFR., Data suggest growth hormone (GH) potentiates estradiol effects on proliferation in breast cancer cells expressing high levels of GHR; GH/GHR signaling overcomes antiproliferative effect of insulin-like growth factor I receptor tyrosine kinase inhibition., results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer, Data suggest that the down-regulation of insulin-like growth factor I receptor (IGF-IR) expression could be a specific molecular target for hepatoma cell proliferation., High circulating IGF1 concentrations and mucosal IGF1R expression may play important roles in both the formation and development of colorectal carcinoma., an important role for PTP1B as a negative regulator of BRK and IGF-1Rbeta signaling in ovarian cancer cells., High membranous/cytoplasmic pIGF1R expression is associated with brain metastases., Data indicate that combination therapy of IGF receptor (IGFR) inhibitors with other molecular targeted agents (MTA) may improve the therapeutic efficacy in hepatocellular carcinoma (HCC)., These results clarify the relationship between ER-alpha and PDZK1, propose a direct relationship between PDZK1 and IGF1R, and identify a novel oncogenic activity for PDZK1 in breast cancer., ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile., These results suggest an important role for TGF-beta1 in osteosarcoma cell growth, with the induction of IGFBP-3 by TGF-beta1 serving in a negative-feedback loop to control cell growth by preventing activation of the IGF1R., inhibition of IGF-IR and targeting of the JAK2/STAT3 signaling pathway can be a target for ovarian cancer therapy., Data from knockout/transgenic mice suggest that neither IGF1R (human or mouse) nor Ghr (growth hormone receptor) signaling is required for postnatal skeletal muscle development or for regeneration in response to cardiotoxin injury., Network models inferred from the data revealed a conserved set of signaling pathways and RTK-specific features that grouped the RTKs into three distinct classes, The consequent increase in IGF-IR mRNA stability., Report co-expression of IGF-1R and ALK in embryonal and alveolar rhabdomyosarcoma and suggest both as possible drug targets., there is a rethinking as to where and how IGFR-1 inhibition can be effectively harnessed as an antineoplastic tool, rs4966014 was associated with left ventricular hypertrophy in type 2 diabetic patients., Phosphorylation of P-Rex1 at serine 1169 participates in IGF-1R signaling in breast cancer cells., PDGFRalpha and IGF-1R are dynamically regulated and distributed in nucleus and cytoplasm in alveolar Rhabdomyosarcoma., IGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer., demonstrated that let-7a1-mediated IGF1R downregulation was accompanied by attenuation of Elk1 activity and c-fos expression, inhibition of cell proliferation, enhanced apoptosis and cell cycle arrest, miR-486 directly targets components of insulin growth factor (IGF) signaling including IGF1, IGF1 receptor, and phosphoinositide-3-kinase, regulatory subunit 1alpha (PIK3R1, or p85a) and functions as a potent tumor suppressor of lung cancer., Low PTEN protein expression significantly increases the risk of lethal prostate cancer, particularly when the IGF-IR expression remains at normal level., Results indicated that systemic lupus erythematosus activity is affected by a modulation of the insulin-like growth factor-1 signal pathway and +3179G/A IGF-1R polymorphism., there was no obvious correlation between IGF-1R expression and patient survival., The sole presence of erlotinib was capable of rapidly activate an IGF-1R-dependent, vimentin-enriched mesenchymal-like phenotype in delE746-A750-mutated epithelial cells., FBLN3 suppresses both epithelial-to-mesenchymal transition and self-renewal of lung cancer stem cells by modulating the IGF1R pathway., The IGF axis might play a key role in tumor progression of esophageal carcinomas. The IGF-IR targeting strategies might thus be useful anticancer therapeutics for human esophageal malignancies., Type I IGFR is autophosphorylated in brain-seeking breast cancer cells., Data indicate that miR-140 downregulates insulin-like growth factor 1 receptor (IGF1R) by directly targeting its 3' untranslated regions (3' UTR)., Simultaneously blocking EGFR, IGF1R and Bcl-xl genes is capable of altering the balance between proliferating versus apoptotic and senescent cells in the favor of both of apoptosis and senescence and, therefore, the tumor cells regression., Experiments confirmed that combined inhibition of CDK4 and IGF1R cooperatively suppresses the activation of proteins within the AKT pathway, Rescue experiments showed that ectopic expression of IGF1R significantly promoted the proliferation of ovarian cancer cells stably overexpressing miR-133a, IGF-IR stabilizes the beta1 subunit by protecting it from proteasomal degradation, a major activity of DNp73 is to establish initiation of the invasion-metastasis cascade via EPLIN-dependent IGF1R regulation, Data indicate that IGF-1R influences double-strand break (DSB) repair by both major DSB repair pathways., Immunohistochemical staining for EGFR, HER2 and IGF-1R was undertaken in 31 ovarian adult granulosa cell tumors. Tumor DNA was also analysed for mutations in the tyrosine kinase domain of EGFR (exons 18-21)., Activation of IGF-1R can induce apoptosis in adipose-derived stem cells, whereas it can be prevented by the A20 and osteocalcin expression., The rs1976667 and rs2684788 loci of the human IGF-1R gene are likely associated with different genetic susceptibilities to idiopathic short stature., HER2 and IGF-IR may be clinically beneficial in minimizing the acquired resistance to trastuzumab therapy., Inhibition of miR-223 was found to maintain the undifferentiated state of hESCs, while addition of miR-223 induced differentiation. Furthermore, these effects were found to be likely dependent on IGF-1R/Akt signaling, Integrated p38 MAPK and IGF-1R signals inversely control STAT3 activity to maintain human dental pulp stem cells quiescence and activation., Data indicate that the blockade of IGF-I receptor (IGF-IR) and ErbB3 receptor (ErbB3) survival pathways and downstream resistance mechanisms was achieved with MM-141., LKB1 expression in cancer cell resulted in dephosphorylation of several tumor-enhancing RTKs, including ErbB2, hepatocyte growth factor receptor (c-Met), EphA2, rearranged during transfection (RET), and insulin-like growth factor I receptor., that platelet-released miR-223 promotes advanced glycation end product-induced vascular endothelial cell apoptosis via targeting insulin-like growth factor 1 receptor., decoy nucleotides which were complementary to the 5', central or 3' region of mature miR-223 suppressed miR-223 targeting the 3'UTR of IGF1R., a key player in mediating Tissue Factor/ Factor VIIa-induced cell survival, investigate the expression of IGF-1, IGFBP-3 and IGF-1R in STRO-1-positive dental pulp stem cells (DPSCs) and fully impacted wisdom teeth in relation to tooth development, The expression pattern of IGF-1R in archival tissue samples of hepatic metastasis from 24 patients was analyzed by immunohistochemistry., miR-503 is a tumor suppressor for glioblastoma and a favorable factor against glioma progression through targeting IGF-1R., In epiretinal membranes (ERMs), IGF1 and IGF1R mRNA levels were significantly higher in patients with diabetes compared to control subjects., this case-control study demonstrates statistically significant associations between breast cancer risk and polymorphisms in IGF1R gene., miR-99a functions as a tumor metastasis suppressor in Oral squamous cell carcinoma cells and mutually regulates IGF1R, Targeting the IGF-1R/Akt pathway with glucosamine may be an effective therapeutic strategy for treating some type of cancer., IGF1R activation is a molecular mechanism that confers acquired resistance to erlotinib in lung cancers with the wild-type EGFR, Hypoxia increased the population of lung cancer stem cells resistant to gefitinib in EGFR mutation-positive non-small cell lung cancer by activating IGF1R., IGF-1R expression is correlated with positive outcome in patients with classical Hodgkin lymphoma., Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R., Data indicate that the inhibitor of DNA binding 1 (Id1)-IGF-II-IGF-IR-AKT signaling cascade plays an important role in esophageal cancer progression., Aberrant expression of components of the IGF1R pathway is associated with better clinical outcomes in women with luminal A and B, node positive, early breast cancer., our findings suggest miR-630 as a key regulator of cancer cell progression in HER2 over-expressing breast cancer, through targeting of IGF1R., Plasma IGF-1R displayed a potential value for distinguishing pancreatic lesions and could be a new biomarker for guiding TNM stage of pancreatic cancer., Different insulin receptor family expression levels were measured in six cancer cell lines., IGF1R overexpression was a significant predictor of overall survival in patients with transitional cell bladder cancer., Loss of Klotho protein expression, klotho promoter hypermethylation, high miR-504 levels, and high phospho-IGF-1R levels significantly correlated with poor survival, high clinical and pathological stages in pancreatic ductal adenocarcinoma patients, single nucleotide polymorphisms and mutations in the insulin-like growth factor 1 receptor can be detected and may harbor prognostic value in non-small cell lung cancers, The results may suggest that the IGF-IR AA polymorphism is beneficial for endurance-type sports, but is not associated with elite endurance performance. In contrast, the presence of the AA genotype may be a disadvantage in power sports., MRNA levels of IGF-1 and IGF-1R were significantly higher in colorectal cancer tissue compared with its non tumor tissue in patients with and without type 2 diabetes., genetic polymorphism is associated with hepatitis B virus-related hepatocellular carcinoma, proliferation of young and aged human dermal fibroblasts in 3D collagen and its association with baseline levels of IGF1R expression were measured, suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and vegf genotype, Overexpression of IGF1R increased cell proliferation, colony formation, migration, invasion and resistance to apoptosis in prostate cancer., the significance of IGF-1R in pancreatic cancer, Increased expression of IGF1R is associated with oral squamous cell carcinoma., results support growth-promoting role of IGF system in placental/fetal development and suggest that IGF1R and IGFBP3 DNA methylation profiles are dysregulated in maternal impaired glucose tolerance, potentially affecting the fetal metabolic programming, Changes in IGF-1 and IGF-1R on monocytes and granulocytes seem to be part of the mechanism that facilitates recovery from resistance exercise during earlier stages of muscle recovery., Data indicate that insulin-like growth factor 1 receptor (IGF1R) was a target of miR-195 in non-small cell lung cancer (NSCLC)cells., Taken together, topographic and functional interactions between dynactin, importin-beta and RanBP2 are involved in nuclear translocation of IGF-1R., High IGF1R mRNA expression is associated with advanced non-small cell lung cancer., IL6 stimulated SOD2 expression that, at least partially, contributed to the low level of ROS that would likely result in a sustained increase in the expression of IGF-1R through abolishment of beta-arrestin1 in docetaxel resistant cells., there is no evidence that IGF2 methylation was influenced by SNPs within the IGF1, IGF1R or IGF2R genes, which lie on other chromosomes., Data indicate that engineered ubiquitin ligase is an effective therapeutic strategy for the treatment of the cancers with co-expressed insulin receptor/insulin-like growth factor receptor (IR/IGF-1R)., MET, HER3, IGF1R, and INSR pathways activation represent novel mechanism underlying lapatinib unresponsiveness in HER2+ gastric cancer. Combination strategy may be recommended in treating patients with HER2+ gastric cancer with these pathways activation, Suggest that combined IGF1R inhibitor and methyl jasmonate administration may constitute an attractive modality for treating endometrial cancer., miR-145 may inhibit bladder cancer initiation by affecting IGF-IR signaling, strong and differential expression of IGF-1R in different histological degrees of cutaneous squamous cell carcinoma indicates a possible role for IGF-insulin receptor in the carcinogenesis and differentiation of this disease, Our work provides evidence supporting a link between IGFIR and IR isoform expression levels and colorectal adenoma risk., analysis of IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment, The higher protein content and response to IGF-I of IGF-IR, IRS-1, and AKT observed in small for gestational age placentas may represent a compensatory mechanism in response to fetal growth restriction., Data indicate that glycogen synthase kinase 3 beta (GSK3beta) and transcription factors FOXO1/3/4 promote hepatoma cell proliferation through type I insulin-like growth factor receptor (IGF-IR)., There was also no correlation with IGF1R expression and survival in non-small cell lung cancer., Low IGF-1R expression is associated with squamous cell tumours in non-small-cell lung cancer., The presented data subclassified colorectal cancers (CRCs) based on their activated signaling pathways and identify a role for c-MET and IGF1R-driven PI3K signaling in CRCs, which is superior to KRAS mutational tests alone., The data identifies IRAIN as a new imprinted long noncoding RNA originating from the IGF1R promoter., Results demonstrate that miR-194 affected the growth and metastasis of osteosarcoma cells both in vitro and in vivo suggesting that miR-194 functions as tumor suppressor gene probably by downregulating CDH2 and IGF1R., IGF1R polymorphisms and abnormal microRNA expression did not correlate with IGF1R upregulation in adrenocortical tumors., the quantitative balance between insulin-like growth factor (IGF)-1 ligand, receptor, and binding protein levels in ovarian cancer cells, High IGF1R expression was associated with glioma., High IGF1R gene copy number and protein overexpression are frequent in non-small cell lung carcinoma but they are not prognostically relevant., Expression of IGF-1R in gastric cancer is associated with lymph node metastasis, is correlated with worse prognosis and high histological malignancy grade, and is an independent predictor of survival in patients with gastric cancer., Growth retardation in our patients is likely caused by the IGF1R mutation that might predispose to disturbances of carbohydrate homeostasis., Expression of IGF-1R is higher in esophageal squamous cell carcinoma than in adjacent normal tissue. In a xenograft model, results suggest the oncogenic function of IGF-1R in regulating cell proliferation, clonogenesis, the cell cycle and apoptosis., miR-375 and IGF1R may serve as a novel therapeutic target for laryngeal squamous cell carcinoma., Follow-up replication analyses in up to an additional 21,345 participants identified three new fasting plasma glucose loci reaching genome-wide significance in or near PDK1-RAPGEF4, KANK1, and IGF1R., Results indicate that IGF-1R +3179G>A polymorphism plays an important role in progression of colorectal cancer., A soluble IGF-1R extracellular domain fragment (sol IGF-1R) interacts with GHR in response to GH., Additive impact of HER2-/PTK6-RNAi on interactions with HER3 or IGF-1R leads to reduced breast cancer progression, Picropodophyllin causes tumor cell mitotic arrest and catastrophe by depolymerizing microtubules via IGF-1 receptor-independent mechanism., The expression of let-7b-5p was remarkably reduced in multiple myeloma tissues and cell lines, and the mRNA and protein levels of IGF1R in the RPMI-8226 cell line were down-regulated by let-7b-5p., Our data indicated that let-7i might control T cells fates in AS by targeting IGF1R., P-cadherin is able to potentiate ligand-dependent signaling of insulin-like growth factor 1 receptor in malignant keratinocytes and epidermal growth factor receptor in dysplastic cells., Silencing insulin-like growth factor-1 receptor expression inhibits gastric cancer cell proliferation and invasion., Data demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R), TM4SF4 expression was correlated with the increased expression of IGF1, consequently resulting in IGF1R activation in lung adenocarcinoma., In a population of Chinese patients with gastric cancer, IGF1R was found to be highly expressed and associated with poor prognosis., Association between insulin-like growth factor-1 receptor (IGF1R) negativity and poor prognosis in a cohort of women with primary breast cancer., T-cadherin regulates prostate cancer cell behavior by tuning the balance in EGFR/IGF-1R activity and enhancing the impact of IGF-1R, Data indicate that insulin-like growth factor 1 receptor (IGF-1 influences repair of endogenous DNA damage., Cotargeting IGF-1R and HER2 resulted in significant growth inhibition in breast cancer cells., miR-7 inhibits cellular growth and glucose metabolism in gliomas, at least partially, by regulating the IGF-1R/Akt signaling pathway., Suggest IGF1R positive expression as an unfavorable factor for disease-free survival in NSCLC patients. IGF1R expression was associated with smoking status and tumor size., (99m)Tc-ZIGF1R, IGF1R may have a role in hypoxia-induced cancer progression and metastasis mediated by epithelial-mesenchymal transition, IGF-1R expression level may serve as a predictive biomarker for radiosensitivity of rectal cancer before preoperative radiotherapy., The miR-143/145 cluster acts as a tumor suppressor in colorectal cancer through the inhibition of IGF1R translation., Basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474., Our findings suggested that hsa-miR-143 could modulate cisplatin resistance of human gastric cancer cell line at least in part by targeting IGF1R and BCL2., These experiments revealed that the C-terminal activating region 2 domain of Epstein-Barr virus LMP1 increased the mRNA expression and the secretion of the ligand IGF1, which promoted phosphorylation of IGF1R., IGF1R is a direct target of mir-323-5p and its targeting results in increased apoptosis and decreased cell proliferation and migration in a glioma cell line., The concurrent expression of OCT4/NANOG/IGFIR was mostly confined to hepatitis B virus (HBV)-related HCC (HBV-HCC) and was significantly correlated with early tumor recurrence., Results show gene amplification of IGF1R and EGFR exclusively in malignant cases of phyllodes tumors suggesting a potential use as therapeutic targets., It is reported here that both splice variants of insulin/IGF1 receptor hybrids are activated by IGF1 with >20-fold higher potency than insulin., The data demonstrate that miR-145 influences embryo attachment by reducing the level of IGF1R in endometrium., Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS., IGF-1R expression was a negative predictive factor for a response to EGFR-TKIs in NSCLC patients harboring activating EGFR mutations., Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients, Upregulation of IGF-1R expression after neoadjuvant treatment is a poor prognostic factor in breast cancer patients, providing a rationale for incorporating anti-IGF-1R drugs in the management of these patients., IGF1R-mediated tyrosine phosphorylation pathway may play important roles in the regulation of sperm capacitation in humans., show that adipogenic differentiation requires primary cilia elongation associated with the recruitment of IGF-1Rbeta onto the cilium, The present study revealed the pleiotropic impact of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on IGF-1R, and an inducing effect on IGF-II and IGFBP-3 in hepatocellular carcinoma., The insulin receptor and IGF1 receptor kinase domains are functional dimers in the activated state., Suggest that miR-133a is downregulated in gastric cancer and functions as a tumor suppressor in vitro and in vivo partly by repressing IGF1R., IGF1R may play an important role in CLL biology, in particular in aggressive CLL clones characterized by IGHV-UM, trisomy 12 and NOTCH1 mutation, it was concluded that TGF-beta1, IGF-I/IGF-IR and VEGF-A overexpression is associated with the presence of aggressive tumors, which exhibit an increased probability of metastasis, a poor response to treatment and reduced survival rate., Report expression of IGF1R transcripts in HCV infected patients., Our results suggest that metformin is a potent inhibitor of the IGF-1/IGF-1R system and may be beneficial in prostate cancer treatment., The aberrant decreases in Ik-1 and MZF1 contribute significantly to the pathogenesis of NPM-ALK(+) T-cell lymphoma through the upregulation of IGF-IR expression., Overall survival (OS) and disease-specific survival (DSS) were reduced in patients whose tumors contained high membrane IGF-1R., This study suggests that IGF-1R expression could be associated with better clinical outcome in classical Hodgkin's lymphoma but is significantly associated with the expression of MET receptor., Our results suggest that the decreased expression of IGF1-R by malignant plasma cells is a prognostic factor associated with severe disease, The results demonstrate that miR-30a influences non-small cell lung cancer progression through PI3K/AKT signaling pathway by targeting IGF1R in A549 cells., These results showed that deguelin possessed antitumor effect by targeting Akt in dual axis such as EGFR and IGF1R signaling pathways and suggested that it provides an applicable therapeutic strategy for HNSCC patients., Absence or low expression of IGF-1R was associated with high grade- and advanced tumors. IGF-1R might be a tumor marker in Barrett's esophagus since a change in expression patterns was found in the course from normal esophageal tissue to adenocarcinoma., The authors show that decreased H19 long noncoding RNA increases microRNA let-7 activity, which in turn inhibits Igf1r expression at the post-transcriptional level, thereby contributing to reduced proliferation of endometrial stromal cells., Our results indicated that miR-139-5p acts as a tumor suppressor in non-small cell lung cancer partially via down-regulating IGF1R expression., PTEN regulates IGF-1R-mediated therapy resistance in melanoma, CAV1 expression was positively related to IGF-1R expression in human hepatocellular carcinoma tissues; CAV1 confers resistance of hepatoma cells to anoikis by activating IGF-1 pathway., Our study found that breast cancer with T2DM had a higher expression of IGF1R, and the higher IGF1R was associated with negative Her2 expression., These findings suggest that miR-133a may act as a tumor suppressor and inhibited survival of hepatocellular carcinoma cells by targeting IGF-1R, EGFR and IGF-1R appear to be overexpressed in a subset of ampullary adenocarcinomas., Both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells., PARP regulates estradiol-mediated cell growth by controlling the ER/IGF-1R/PDZK1 axis., Suggest role for EphB4/IGF1R signaling in regulation proliferation/migration of breast cancer cells., Knockdown of IGFqR inhibits colorectal cancer cell growth and decreases WNT/Beta-catenin signal pathways., High expression of IGF1R is associated with triple negative breast cancer., This study defines a clinically recognizable incomplete dominant form of SHORT syndrome, and provides relevant insights into the pathophysiological and phenotypical consequences of IGF1R mutations., Results indicate that increased IGF-1 levels after recurrent hippocampal neuronal firings might, in turn, promote seizure activity via IGF-1R-dependent mechanisms., IGF-IR is an independent prognostic factor associated with shorter survival in glioblastoma., Down-regulation of IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments, results in decreased downstream signaling., Polymorphisms in MAP3K3, MMP24 and IGF1R are associated with greater height and act additively on height in children of an admixed population., Reducing the IGF-1 signaling pathway exerts a neuroprotective effect in a transgenic mouse model of spinal muscular atrophy., IGF1R overexpression is considered a useful independent predictor of outcomes in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1., Low EI24 and high IGF-1R expressions in lung cancer patients., remarkable therapeutic window observed for BI 885578 is achieved by virtue of the distinctive pharmacokinetic properties of the compound capitalizing on the physiologic mechanism of glucose homeostasis and differential levels of IGF1R and INSR expression, Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL, Data suggest that temozolomide (TMZ) resistance associates with insulin like growth factor 1 (IGF-1R) activation, and that simultaneous or prior IGF-1R inhibitors (IGF-1Ri) caused less effective chemo-sensitization., HRD1 interacted with IGF-1R and promoted its ubiquitination and degradation by the proteasome, Mechanistic investigations indicated that DNp73 acted by attenuating expression of miR-885-5p, a direct regulator of the IGF1 receptor (IGF1R) responsible for stemness marker expression., IGF1R as a target of let7a was subsequently validated using the luciferase assay., IGF-1R by miR-122 down-regulation contributed to activation of RAS/RAF/ERK signaling, which was associated with sorafenib resistance in hepatocellular carcinoma., MiRNA-323-5p inhibited human cerebral glioma U373 cell proliferation and promoted its apoptosis by reducing IGF-1R, progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels, we found a SNP (rs2016347) in IGF1R as a potential predictive marker for chemotherapy efficacy in breast cancer patients treated with TAC, High expression of IGF1R is associated with breast cancer., Low-oxygen tension can modify the IGF-1 or IGF-2 signaling via the IGF-1R and IR in placental mesenchymal stem cells., Anoikis resistance of oestrogen-responsive breast cancer cells depends upon IGF activation of the type I IGF receptor and PI3-kinase/Akt pathway., overexpression of the IGF-1R, and activation of GSK3beta and FOXO3a might be the molecular mechanisms underlying the development of liver cirrhosis, Given the limited number of patients treated with KW-2450 in our study, it is not possible to make a meaningful comparison of efficacy with other IGF-1R/IR dual kinases inhibitors, IGF1R signaling was necessary for DC-mediated T-ALL survival., Data indicate that a highly specific qRT-PCR assay to quantify levels of the insulin-like growth factor receptor and insulin receptor isoforms (IR-A, IR-B, and IGF-1R) on the same scale to provide a critical diagnostic and predictive tool., Data show that the lack of insulin like growth factor 1 receptor (IGFIR) resulted in an impaired cold acclimation., Full-length MGF directly stimulates the IGF-IR. Despite a higher EC50 concentration, at high equimolar concentrations full-length MGF showed a similar maximal potency to activate the IGF-IR as compared to IGF-I., Our study demonstrates that the IGF1R/p110b/AKT/mTOR axis confers resistance to BYL719 in PIK3CA mutant breast cancers., IGF1R expression in epithelial ovarian cancer is associated with estrogen and progesterone receptor positive status and HER2 non-amplification., IGF-1 and IGF-1 receptor may be involved in the pathogenesis of Graves' disease; IGF-1 and IGF-1 receptor act by different mechanisms (paracrine vs. autocrine) as suggested by their differential expression in epithelial and stromal cells.,
OMIM_DISEASE Insulin-like growth factor I, resistance to,
SP_COMMENT catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate., disease:Defects in IGF1R may be a cause in some cases of resistance to insulin-like growth factor 1 (IGF1 resistance) [MIM:270450]. IGF1 resistance is a gowth deficiency disorder characterized by intrauterine growth retardation and poor postnatal growth accompanied with increased plasma IGF1., enzyme regulation:Autophosphorylation activates the kinase activity., function:This receptor binds insulin-like growth factor 1 (IGF1) with a high affinity and IGF2 with a lower affinity. It has a tyrosine-protein kinase activity, which is necessary for the activation of the IGF1-stimulated downstream signaling cascade. When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin., online information:IGF-1 receptor entry, PTM:Phosphorylation of Tyr-980 is required for IRS1- and SHC1-binding., PTM:The cytoplasmic domain of the beta subunit is autophosphorylated on tyrosine residues in response to insulin-like growth factor I (IGF I)., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily., similarity:Contains 1 protein kinase domain., similarity:Contains 3 fibronectin type-III domains., subunit:Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Forms a hybrid receptor with INSR, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R., tissue specificity:Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibrobasts, spleen and placenta (at protein level). Expressed in a variety of tissues.,