Role of insulin-like growth factor-binding proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers
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The insulin family of proteins include insulin-like growth factor binding proteins (IGFBPs) that are classified into two groups based on their differential affinities to IGFs: IGF high-affinity binding proteins (IGFBP1-6) and IGF low-affinity IGFBP-related proteins (IGFBP-rP1-10). IGFBPs interact with many proteins, including their canonical ligands insulin-like growth factor 1 (IGF-I) and IGF-II. Together with insulin-like growth factor 1 (IGF1) receptor (IGF1R), IGF2R, and ligands (IGF1 and IGF2), IGFBPs participate in a complex signaling axis called IGF-IGFR-IGFBP. Numerous studies have demonstrated that the IGF-IGFR-IGFBP axis is relevant in gastrointestinal (GI) and other cancers. The presence of different IGFBPs have been reported in gastrointestinal cancers, including esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAD or EAC), and gastric adenocarcinoma (GAD or GAC). A literature-based survey clearly indicates that an urgent need exists for a focused review of the role of IGFBPs in gastrointestinal cancers. The aim of this review is to present the biochemical and molecular characteristics of IGFBPs with an emphasis specifically on the role of these proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers.
KeywordsESCC Esophageal squamous cell carcinoma Esophageal adenocarcinoma Gastric adenocarcinoma IGFBP7 IGFBPs / IGFBP-rP
- EAC or EAD
Esophageal squamous cell carcinoma
- GAC or GAD
Gastrointestinal stromal tumor
Human protein reference database
Insulin-like growth factor
Insulin-like growth factor-binding proteins
IGF low-affinity IGFBP-related proteins
Isobaric tags for relative and absolute quantitation
Stable isotope labeling by amino acids in cell culture
The author apologizes to all colleagues whose work could not be cited due to space limitations. The IHC data in Fig. 1 was used with prior permission from Kashyap et al. from the research article in IOS Press publication (2012–2013: Evaluation of protein expression pattern of stanniocalcin 2, insulin-like growth factor-binding protein 7, inhibin beta A, and four and a half LIM domains 1 in esophageal squamous cell carcinoma. Cancer Biomarkers 12(1):1–9.). MKK was supported by the Indian Council of Medical Research, New Delhi (IRIS ID: 2006-02010, ICMR).
Conflicts of interest
- 7.Doyle SL, Donohoe CL, Finn SP, Howard JM, Lithander FE, Reynolds JV, et al. IGF-1 and its receptor in esophageal cancer: association with adenocarcinoma and visceral obesity. Am J Gastroenterol. 107:196–204.Google Scholar
- 8.Huang XP, Zhou WH, Zhang YF. Genetic variations in the IGF-IGFR-IGFBP axis confer susceptibility to lung and esophageal cancer. Genet Mol Res. 13:2107–2119.Google Scholar
- 9.Ong J, Salomon J, te Morsche RH, Roelofs HM, Witteman BJ, Dura P, et al. Polymorphisms in the insulin-like growth factor axis are associated with gastrointestinal cancer. PLoS One. 9:e90916.Google Scholar
- 10.Smith E, Ruszkiewicz AR, Jamieson GG, Drew PA. IGFBP7 is associated with poor prognosis in oesophageal adenocarcinoma and is regulated by promoter DNA methylation. Br J Cancer. 110:775–782.Google Scholar
- 19.Trent JC, Ramdas L, Dupart J, Hunt K, Macapinlac H, Taylor E, et al. Early effects of imatinib mesylate on the expression of insulin-like growth factor binding protein-3 and positron emission tomography in patients with gastrointestinal stromal tumor. Cancer. 2006;107:1898–908.CrossRefPubMedGoogle Scholar
- 20.Yang HP, Liu JF, Rao J, Zhang XM, Qian HL, Niu XQ, et al. (2014) Insulin-like growth factor binding protein-3 (IGFBP-3) genetic variant and the risk of esophageal squamous cell carcinoma in a Chinese population. Genet Mol Res. 13:4146–4153.Google Scholar
- 21.McElholm AR, McKnight AJ, Patterson CC, Johnston BT, Hardie LJ, Murray LJ. (2010) A population-based study of IGF axis polymorphisms and the esophageal inflammation, metaplasia, adenocarcinoma sequence. Gastroenterology. 139:204–21.Google Scholar
- 24.Sato Y, Inokuchi M, Takagi Y, Otsuki S, Fujimori Y, Yanaka Y, et al. Relationship between expression of IGFBP7 and clinicopathological variables in gastric cancer. J Clin Pathol. 2015. doi: 10.1136/jclinpath-2015-202987.
- 27.Kashyap MK, Pawar HA, Keerthikumar S, Sharma J, Goel R, Mahmood R, et al. Evaluation of protein expression pattern of stanniocalcin 2, insulin-like growth factor-binding protein 7, inhibin beta A and four and a half LIM domains 1 in esophageal squamous cell carcinoma. Cancer Biomark. 2013;12:1–9.CrossRefGoogle Scholar
- 28.Yanbin JWDYC, Yan Y. No association between two SNPs in the IGFBP1 gene and esophageal squamous cell carcinoma. J Baotou Med Coll. 2009;25:2001.Google Scholar
- 29.Hu YC, Lam KY, Law S, Wong J, Srivastava G. Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC. Clin Cancer Res. 2001;7:3519–25.PubMedGoogle Scholar
- 30.Subbannayya Y, Mir SA, Renuse S, Manda SS, Pinto SM, Puttamallesh VN, et al. Identification of differentially expressed serum proteins in gastric adenocarcinoma. J Proteomics. 2015. doi: 10.1016/j.jprot.2015.04.021.
- 36.Siahpush SH, Vaughan TL, Lampe JN, Freeman R, Lewis S, Odze RD, et al. Longitudinal study of insulin-like growth factor, insulin-like growth factor binding protein-3, and their polymorphisms: risk of neoplastic progression in Barrett’s esophagus. Cancer Epidemiol Biomarkers Prev. 2007;16:2387–95.CrossRefPubMedGoogle Scholar
- 67.Tennant MK, Thrasher JB, Twomey PA, Birnbaum RS, Plymate SR. Insulin-like growth factor-binding proteins (IGFBP)-4, -5, and -6 in the benign and malignant human prostate: IGFBP-5 messenger ribonucleic acid localization differs from IGFBP-5 protein localization. J Clin Endocrinol Metab. 1996;81:3783–92.PubMedGoogle Scholar
- 69.Miyake H, Nelson C, Rennie PS, Gleave ME. Overexpression of insulin-like growth factor binding protein-5 helps accelerate progression to androgen-independence in the human prostate LNCaP tumor model through activation of phosphatidylinositol 3′-kinase pathway. Endocrinology. 2000;141:2257–65.PubMedGoogle Scholar
- 74.Braulke T, Dittmer F, Gotz W, von Figura K. Alteration in pancreatic immunoreactivity of insulin-like growth factor (IGF)-binding protein (IGFBP)-6 and in intracellular degradation of IGFBP-3 in fibroblasts of IGF-II receptor/IGF-II-deficient mice. Horm Metab Res. 1999;31:235–41.CrossRefPubMedGoogle Scholar
- 79.Wu C, Kraft P, Zhai K, Chang J, Wang Z, Li Y, et al. (2012) Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. Nat Genet. 44:1090–1097.Google Scholar