Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment

Abstract

Insulin-like growth factor 2 (IGF2) is a strong mitogenic peptide with an imprinted gene that is primarily involved in fetal development. It is highly expressed in the fetus where it is involved in fetal growth and tissue differentiation. However, postnatally, the expression of IGF2 decreases despite higher expression levels in the blood as compared with that of IGF1. In adults, the physiological function of IGF2 is poorly understood; however, the possibility of a metabolic function exists. Although the expression of IGF2 normally decreases in adults, it is overexpressed in a variety of cancers and associated with increased insulin-like growth factor 1 (IGF1R) receptor and insulin receptor (IR) activity. This subsequently increases the activity of downstream genes such as AKT, FOXO, and MAPK, resulting in enhanced proliferation, survival, and overall worse prognosis in patients overexpressing IGF2. As IGF1R activation has been found in several types of cancers, many different IGF1R-targeted therapies have been clinically evaluated, however, with only limited anti-cancer efficacy. In the present review, the physiological function of IGF2 will be outlined in relation to gene expression, imprinting, and signaling. Additionally, differences in physiological and aberrant signaling of IGF2 in cancer will be summarized.

A Case Report of Doege–Potter Syndrome: A Rare Cause of Hypoglycemia in a Patient without Diabetes

“…Pro-IGF-2 is first glycosylated in the E domain, then cleaved by a convertase to form mature IGF-2. In NICTH the convertase does not completely cut the E-domain resulting in a longer peptide called “big-IGF-2” [ 5 ]. IGF-2 and big-IGF-2 can interact with several receptors: IGF receptor 1, IGF receptor 2, insulin receptor type A and B and hybrid receptors that bind both IGF and insulin with several affinities.…”