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Role of insulin-like growth factor-binding proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers

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  • Published:
Tumor Biology

Abstract

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.

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Abbreviations

EAC or EAD:

Esophageal adenocarcinoma

ESCC:

Esophageal squamous cell carcinoma

GAC or GAD:

Gastric adenocarcinoma

GIST:

Gastrointestinal stromal tumor

HPRD:

Human protein reference database

IGF:

Insulin-like growth factor

IGFBPs:

Insulin-like growth factor-binding proteins

IGFBP-rPs:

IGF low-affinity IGFBP-related proteins

iTRAQ:

Isobaric tags for relative and absolute quantitation

SILAC:

Stable isotope labeling by amino acids in cell culture

SP:

Signal peptide

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Acknowledgments

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).

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  1. Moores Cancer Center, University of California San Diego, 3855 Health Science Drive, La Jolla, CA, 92093-0820, USA

    Manoj K. Kashyap

  2. Department of Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India

    Manoj K. Kashyap

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Kashyap, M.K. Role of insulin-like growth factor-binding proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers. Tumor Biol. 36, 8247–8257 (2015). https://doi.org/10.1007/s13277-015-3972-3

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