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Overlaps Between the Insulin and IGF-I Receptor and Cancer

  • Antonino BelfioreEmail author
  • Roberta Malaguarnera
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Dysregulation of the insulin growth factor (IGF) system is implicated in various aspects of cancer. Notably, the physiological signaling specificity existing between insulin and insulin-like growth factors I and II (IGFs) is often disrupted in cancer by various mechanisms. These may include overexpression of IGFs and of IGF-I receptors (IGF-IR), aberrant expression of insulin receptor isoform A, and appearance of atypical receptors that bind both insulin and IGFs. Enhanced cross talk between insulin and the IGF-I receptors may also result from insulin resistance and chronic hyperinsulinemia, newly recognized risk factors for cancer. All these factors associated with reduced signaling specificity between insulin and IGFs may also activate unbalanced intracellular signaling more strongly coupled to protumoral biological effects than to metabolic effects. A better knowledge of the molecular mechanisms involved may have profound implications in cancer prevention and therapy.

Keywords

Insulin Resistance Insulin Receptor Insulin Growth Factor Compensatory Hyperinsulinemia Insulin Target Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

IGF

Insulin growth factor

IR

Insulin receptor

IGF-IR

IGF-I receptor

IGFBP

IGF-binding protein

IRS-1 and -2

Insulin receptor substrates 1 and -2

HR

Hybrid receptor

GH

Growth hormone

MAPK

Mitogen-activated protein kinase

PI3K

Phosphatidylinositol 3-kinase

NEFA

Nonesterified fatty acids

PKC

Protein kinase C

T2DM

Type 2 diabetes mellitus

M6P/IGF-IIR

Mannose-6-phosphate/IGF-II receptor

Notes

Acknowledgments

This work was partially supported by grants from the AIRC (Associazione Italiana per la Ricerca sul Cancro) and PRIN-MIUR 2008 (Ministero Italiano Università e Ricerca) to A.B.

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Endocrinology, Department of Clinical and Experimental MedicineUniversity of CatanzaroCatanzaroItaly

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