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Gene Review

IGF1R  -  insulin-like growth factor 1 receptor

Homo sapiens

Synonyms: CD221, IGF-I receptor, IGFIR, IGFR, Insulin-like growth factor 1 receptor, ...
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Disease relevance of IGF1R

  • A single patient with Beckwith-Wiedemann Syndrome (BWS) demonstrated monoallelic expression of the maternally derived IGF1R allele in normal kidney, associated Wilms' tumour and in peripheral blood lymphocytes [1].
  • We have previously shown that a chimeric single-chain antibody against IGF1R (scFv-Fc) and a murine antibody EM164 down-regulate IGF1R, making breast cancer cells unresponsive to IGF-I [2].
  • In four cases, IGF1R and IRS-1 levels were lower in the metastases than in the primary tumors [3].
  • The IGF1R was significantly up-regulated at the protein and mRNA level in primary prostate cancer compared with benign prostatic epithelium [3].
  • Transgenic mice overexpressing IGF1R in the heart displayed cardiac hypertrophy, which was the result of an increase in myocyte size, and there was no evidence of histopathology [4].
  • To validate the IGF1R pathway as a potential target in MPNSTs, we first confirmed that high IGF1R protein correlated with worse tumor-free survival in an independent set of samples using IHC [5].

Psychiatry related information on IGF1R


High impact information on IGF1R


Chemical compound and disease context of IGF1R


Biological context of IGF1R

  • These findings challenge earlier reports of IGF1R down-regulation in metastatic disease and reinforce the importance of the IGF1R in prostate cancer biology [3].
  • The type 1 insulin-like growth factor receptor (IGF1R) mediates tumor cell growth, adhesion, and protection from apoptosis [3].
  • Our data show that IGF1R can regulate several aspects of the malignant phenotype [19].
  • The type 1 insulin-like growth factor receptor (IGF1R) is required for growth, tumorigenicity and protection from apoptosis [20].
  • OBJECTIVE: We studied clinical and in vitro aspects of a human IGF1R gene dosage effect [21].

Anatomical context of IGF1R


Associations of IGF1R with chemical compounds

  • However, IGF1R gene silencing was capable of inducing significant inhibition of survival, enhancement of apoptosis, and approximately two-fold sensitization to cisplatin and temozolomide [27].
  • The type 1 IGF receptor (IGF1R) is a transmembrane tyrosine kinase that is frequently overexpressed by tumours, and mediates proliferation and apoptosis protection [28].
  • In both DU145 and PC3, IGF1R knockdown led to enhancement of sensitivity to mitoxantrone, etoposide, nitrogen mustard and ionizing radiation [29].
  • Disruption of IGF-II/IGF1R interaction appears to be the main mode of action of suramin since the suramin response was abolished in the presence of the IGF1R blocking antibody, alpha IR-3 [30].
  • Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit [31].
  • Fibronectin-induced adhesion is mediated through beta1 integrin receptor and is IGF-IR-independent [32].

Physical interactions of IGF1R

  • These data suggest that the positive charges in the C- and D-regions of IGF-1 contribute significantly to the binding preference of the IGF-1R for IGF-1 [33].
  • We conclude that SOCS-3 binds to the IGFIR and may be a direct substrate for the receptor tyrosine kinase [34].
  • Furthermore IGF-binding proteins are specific for IGF-I and IGF-II thereby modulating the binding of the IGFs to the IGF-I receptor [35].
  • In addition, IGF1R down-regulation increased insulin binding consistent with the formation of an increased number of holo-IR on the cell surface [36].
  • RACK1 also interacted with the IGF-1R in fibroblasts and MCF-7 cells and with endogenous insulin receptor in COS cells [37].

Enzymatic interactions of IGF1R


Regulatory relationships of IGF1R

  • We previously showed that IGF1R knockdown blocked survival of prostate cancer cells in which Akt activation was deregulated by PTEN loss [27].
  • Luteolin inhibited insulin-like growth factor 1 (IGF-1) induced activation of IGF-1R and AKT in prostate cancer PC-3 and DU145 cells [40].
  • We found that human SOCS-3 protein interacts directly with the cytoplasmic domains of the activated IGFIR and the insulin receptor (IR) in the yeast two-hybrid assay [34].
  • To mimic IGF-1R expression levels in CD28-stimulated Jurkat cells these cells were stably transfected to over-express the IGF-1R [41].
  • In a yeast two-hybrid screen of a human fetal brain library, we have previously identified SOCS-2 as a binding partner of the activated IGF-I receptor (IGFIR) [34].

Other interactions of IGF1R

  • Around midgestation a separate IGF-1 receptor, indicated by the preferential displacement of iodinated IGF-1 by IGF-1, appeared [42].
  • Shc immunoprecipitates performed after IGF-1 stimulation contain coprecipitated EGFR, suggesting that IGF-1R activation induces the assembly of EGFR.Shc complexes [43].
  • Alanine substitution for the positively charged residues in the C- and D-regions of IGF-1 led to 15- and 10-fold losses, respectively, in binding potency for the human IGF-1R, but they increased the potency of binding to the human IR 29- and 6-fold, respectively [33].
  • In HCA7 colon and C4-2 prostate carcinoma cells, ERBB2 is constitutively activated in a ligand-independent manner, whereas IGF1R-beta and PDGFR-beta require ligand interaction for activation [44].
  • {beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase [45].

Analytical, diagnostic and therapeutic context of IGF1R

  • IGF1R-overexpressing MCF7 xenografts in nude mice were visualized at 4, 12, and 24 h after tail vein administration of the (99m)Tc-CCND1 antisense probe but not the control probe [46].
  • It will be important to use data from preclinical and early clinical trials to establish the molecular correlates of sensitivity to IGF1R blockade, and the optimum means of combining this new approach with standard treatment modalities [28].
  • Although multiple receptors for the IGFs have been identified, the IGFs primarily exert their biologic effects through ligation of the type I IGF receptor tyrosine kinase (IGF1R) [47].
  • In this study, we examine the relative expression of the two IGF1R mRNA isoforms by a semiquantitative RT-PCR approach using highly standardized conditions, beta-2 microglobulin (B2M) as a reference gene and gel imaging analysis [31].
  • Scatchard analysis revealed 3- and 5-fold increases in IGF-1R expression by the primary cervical cancer cell cultures and cervical cancer cell lines, respectively, compared with the normal ectocervical cells [48].


  1. The insulin-like growth factor 1 receptor gene is normally biallelically expressed in human juvenile tissue and tumours. Howard, T.K., Algar, E.M., Glatz, J.A., Reeve, A.E., Smith, P.J. Hum. Mol. Genet. (1993) [Pubmed]
  2. Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: implications for anti-insulin-like growth factor therapy in breast cancer. Sachdev, D., Singh, R., Fujita-Yamaguchi, Y., Yee, D. Cancer Res. (2006) [Pubmed]
  3. Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease. Hellawell, G.O., Turner, G.D., Davies, D.R., Poulsom, R., Brewster, S.F., Macaulay, V.M. Cancer Res. (2002) [Pubmed]
  4. The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway. McMullen, J.R., Shioi, T., Huang, W.Y., Zhang, L., Tarnavski, O., Bisping, E., Schinke, M., Kong, S., Sherwood, M.C., Brown, J., Riggi, L., Kang, P.M., Izumo, S. J. Biol. Chem. (2004) [Pubmed]
  5. Genomic and molecular characterization of malignant peripheral nerve sheath tumor identifies the IGF1R pathway as a primary target for treatment. Yang, J., Ylipää, A., Sun, Y., Zheng, H., Chen, K., Nykter, M., Trent, J., Ratner, N., Lev, D.C., Zhang, W. Clin. Cancer Res. (2011) [Pubmed]
  6. Association of insulin-like growth factor-1 receptor polymorphism in dementia. Garcia, J., Ahmadi, A., Wonnacott, A., Sutcliffe, W., Nagga, K., Soderkvist, P., Marcusson, J. Dementia and geriatric cognitive disorders (2006) [Pubmed]
  7. Blockade of the insulin-like growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: new cues into the human disease? Carro, E., Trejo, J.L., Spuch, C., Bohl, D., Heard, J.M., Torres-Aleman, I. Neurobiol. Aging (2006) [Pubmed]
  8. Insulin-like growth factor-I receptor densities in human frontal cortex and white matter during aging, in Alzheimer's disease, and in Huntington's disease. De Keyser, J., Wilczak, N., Goossens, A. Neurosci. Lett. (1994) [Pubmed]
  9. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P.C., Cervera, P., Le Bouc, Y. Nature (2003) [Pubmed]
  10. Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Smith, L.E., Shen, W., Perruzzi, C., Soker, S., Kinose, F., Xu, X., Robinson, G., Driver, S., Bischoff, J., Zhang, B., Schaeffer, J.M., Senger, D.R. Nat. Med. (1999) [Pubmed]
  11. Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I. Rubin, J.B., Shia, M.A., Pilch, P.F. Nature (1983) [Pubmed]
  12. Growth-stimulatory actions of insulin in vitro and in vivo. Straus, D.S. Endocr. Rev. (1984) [Pubmed]
  13. A new concept in neurodegeneration: TNFalpha is a silencer of survival signals. Venters, H.D., Dantzer, R., Kelley, K.W. Trends Neurosci. (2000) [Pubmed]
  14. Insulin-like growth factors in human breast cancer. Ellis, M.J., Jenkins, S., Hanfelt, J., Redington, M.E., Taylor, M., Leek, R., Siddle, K., Harris, A. Breast Cancer Res. Treat. (1998) [Pubmed]
  15. Expression of the insulin-like growth factors and their receptors in term placentas: a comparison between normal and IUGR births. Abu-Amero, S.N., Ali, Z., Bennett, P., Vaughan, J.I., Moore, G.E. Mol. Reprod. Dev. (1998) [Pubmed]
  16. IGF-1 receptor tyrosine kinase inhibition by the cyclolignan PPP induces G2/M-phase accumulation and apoptosis in multiple myeloma cells. Strömberg, T., Ekman, S., Girnita, L., Dimberg, L.Y., Larsson, O., Axelson, M., Lennartsson, J., Hellman, U., Carlson, K., Osterborg, A., Vanderkerken, K., Nilsson, K., Jernberg-Wiklund, H. Blood (2006) [Pubmed]
  17. The cyclolignan PPP induces activation loop-specific inhibition of tyrosine phosphorylation of the insulin-like growth factor-1 receptor. Link to the phosphatidyl inositol-3 kinase/Akt apoptotic pathway. Vasilcanu, D., Girnita, A., Girnita, L., Vasilcanu, R., Axelson, M., Larsson, O. Oncogene (2004) [Pubmed]
  18. Insulin-like growth factor-I receptor signaling in tamoxifen-resistant breast cancer: a supporting role to the epidermal growth factor receptor. Knowlden, J.M., Hutcheson, I.R., Barrow, D., Gee, J.M., Nicholson, R.I. Endocrinology (2005) [Pubmed]
  19. A dominant negative type I insulin-like growth factor receptor inhibits metastasis of human cancer cells. Sachdev, D., Hartell, J.S., Lee, A.V., Zhang, X., Yee, D. J. Biol. Chem. (2004) [Pubmed]
  20. Downregulation of the type 1 insulin-like growth factor receptor in mouse melanoma cells is associated with enhanced radiosensitivity and impaired activation of Atm kinase. Macaulay, V.M., Salisbury, A.J., Bohula, E.A., Playford, M.P., Smorodinsky, N.I., Shiloh, Y. Oncogene (2001) [Pubmed]
  21. Clinical and functional characteristics of the human Arg59Ter insulin-like growth factor i receptor (IGF1R) mutation: implications for a gene dosage effect of the human IGF1R. Raile, K., Klammt, J., Schneider, A., Keller, A., Laue, S., Smith, R., Pfäffle, R., Kratzsch, J., Keller, E., Kiess, W. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  22. Ataxia telangiectasia mutated (Atm) knockout mice as a model of osteopenia due to impaired bone formation. Hishiya, A., Ito, M., Aburatani, H., Motoyama, N., Ikeda, K., Watanabe, K. Bone (2005) [Pubmed]
  23. Multiple signaling pathways are activated during insulin-like growth factor-I (IGF-I) stimulated breast cancer cell migration. Zhang, X., Lin, M., van Golen, K.L., Yoshioka, K., Itoh, K., Yee, D. Breast Cancer Res. Treat. (2005) [Pubmed]
  24. Expression of mRNA for the insulin-like growth factors and their receptors in human preimplantation embryos. Lighten, A.D., Hardy, K., Winston, R.M., Moore, G.E. Mol. Reprod. Dev. (1997) [Pubmed]
  25. Immunohistochemical localization of components of the insulin-like growth factor-system in human deciduous teeth. Götz, W., Krüger, U., Ragotzki, S., Lossdörfer, S., Jäger, A. Connect. Tissue Res. (2001) [Pubmed]
  26. Immunohistochemical localization of components of the insulin-like growth factor system in human permanent teeth. Götz, W., Heinen, M., Lossdörfer, S., Jäger, A. Arch. Oral Biol. (2006) [Pubmed]
  27. Human melanoma cells expressing V600E B-RAF are susceptible to IGF1R targeting by small interfering RNAs. Yeh, A.H., Bohula, E.A., Macaulay, V.M. Oncogene (2006) [Pubmed]
  28. IGF1R signalling and its inhibition. Riedemann, J., Macaulay, V.M. Endocr. Relat. Cancer (2006) [Pubmed]
  29. Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer. Rochester, M.A., Riedemann, J., Hellawell, G.O., Brewster, S.F., Macaulay, V.M. Cancer Gene Ther. (2005) [Pubmed]
  30. Inhibition of insulin like growth factor II autocrine growth of Wilms' tumor by suramin in vitro and in vivo. Vincent, T.S., Hazen-Martin, D.J., Garvin, A.J. Cancer Lett. (1996) [Pubmed]
  31. Differential expression of alternatively spliced mRNA forms of the insulin-like growth factor 1 receptor in human neuroendocrine tumors. Vitale, L., Lenzi, L., Huntsman, S.A., Canaider, S., Frabetti, F., Casadei, R., Facchin, F., Carinci, P., Zannotti, M., Coppola, D., Strippoli, P. Oncol. Rep. (2006) [Pubmed]
  32. Insulin-like growth factor-I receptor mediates the prosurvival effect of fibronectin. Edderkaoui, M., Hong, P., Lee, J.K., Pandol, S.J., Gukovskaya, A.S. J. Biol. Chem. (2007) [Pubmed]
  33. Positively charged side chains in the insulin-like growth factor-1 C- and D-regions determine receptor binding specificity. Zhang, W., Gustafson, T.A., Rutter, W.J., Johnson, J.D. J. Biol. Chem. (1994) [Pubmed]
  34. Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. Dey, B.R., Furlanetto, R.W., Nissley, P. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  35. Signaling via the insulin-like growth factor-I receptor: does it differ from insulin receptor signaling? Blakesley, V.A., Scrimgeour, A., Esposito, D., Le Roith, D. Cytokine Growth Factor Rev. (1996) [Pubmed]
  36. Down-regulation of Type I Insulin-like Growth Factor Receptor Increases Sensitivity of Breast Cancer Cells to Insulin. Zhang, H., Pelzer, A.M., Kiang, D.T., Yee, D. Cancer Res. (2007) [Pubmed]
  37. RACK1 is an insulin-like growth factor 1 (IGF-1) receptor-interacting protein that can regulate IGF-1-mediated Akt activation and protection from cell death. Kiely, P.A., Sant, A., O'Connor, R. J. Biol. Chem. (2002) [Pubmed]
  38. Proinflammatory cytokines block growth of breast cancer cells by impairing signals from a growth factor receptor. Shen, W.H., Zhou, J.H., Broussard, S.R., Freund, G.G., Dantzer, R., Kelley, K.W. Cancer Res. (2002) [Pubmed]
  39. IL-1beta suppresses prolonged Akt activation and expression of E2F-1 and cyclin A in breast cancer cells. Shen, W.H., Jackson, S.T., Broussard, S.R., McCusker, R.H., Strle, K., Freund, G.G., Johnson, R.W., Dantzer, R., Kelley, K.W. J. Immunol. (2004) [Pubmed]
  40. Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells. Fang, J., Zhou, Q., Shi, X.L., Jiang, B.H. Carcinogenesis (2007) [Pubmed]
  41. Insulin-like growth factor-1 activates Akt and Jun N-terminal kinases (JNKs) in promoting the survival of T lymphocytes. Walsh, P.T., Smith, L.M., O'Connor, R. Immunology (2002) [Pubmed]
  42. Ontogenesis of somatomedin and insulin receptors in the human fetus. Sara, V.R., Hall, K., Misaki, M., Fryklund, L., Christensen, N., Wetterberg, L. J. Clin. Invest. (1983) [Pubmed]
  43. Transactivation of the EGF receptor mediates IGF-1-stimulated shc phosphorylation and ERK1/2 activation in COS-7 cells. Roudabush, F.L., Pierce, K.L., Maudsley, S., Khan, K.D., Luttrell, L.M. J. Biol. Chem. (2000) [Pubmed]
  44. Hyaluronan constitutively regulates activation of multiple receptor tyrosine kinases in epithelial and carcinoma cells. Misra, S., Toole, B.P., Ghatak, S. J. Biol. Chem. (2006) [Pubmed]
  45. {beta}-Arrestin is crucial for ubiquitination and down-regulation of the insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3 ligase. Girnita, L., Shenoy, S.K., Sehat, B., Vasilcanu, R., Girnita, A., Lefkowitz, R.J., Larsson, O. J. Biol. Chem. (2005) [Pubmed]
  46. External imaging of CCND1 cancer gene activity in experimental human breast cancer xenografts with 99mTc-peptide-peptide nucleic acid-peptide chimeras. Tian, X., Aruva, M.R., Qin, W., Zhu, W., Duffy, K.T., Sauter, E.R., Thakur, M.L., Wickstrom, E. J. Nucl. Med. (2004) [Pubmed]
  47. The type-1 insulin-like growth factor receptor tyrosine kinase and breast cancer: biology and therapeutic relevance. Gross, J.M., Yee, D. Cancer Metastasis Rev. (2003) [Pubmed]
  48. Overexpression of the insulin-like growth factor-1 receptor and autocrine stimulation in human cervical cancer cells. Steller, M.A., Delgado, C.H., Bartels, C.J., Woodworth, C.D., Zou, Z. Cancer Res. (1996) [Pubmed]
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