IGF2 and cancer

Abstract

Insulin-like growth factor 2 (IGF2) is a 7.5 kDa mitogenic peptide hormone expressed by liver and many other tissues. It is three times more abundant in serum than IGF1, but our understanding of its physiological and pathological roles has lagged behind that of IGF1. Expression of the IGF2 gene is strictly regulated. Over-expression occurs in many cancers and is associated with a poor prognosis. Elevated serum IGF2 is also associated with increased risk of developing various cancers including colorectal, breast, prostate and lung. There is established clinical utility for IGF2 measurement in the diagnosis of non-islet cell tumour hypoglycaemia, a condition characterised by a molar IGF2:IGF1 ratio O10. Recent advances in understanding of the pathophysiology of IGF2 in cancer have suggested much novel clinical utility for its measurement. Measurement of IGF2 in blood and genetic and epigenetic tests of the IGF2 gene may help assess cancer risk and prognosis. Further studies will determine whether these tests enter clinical practice. New therapeutic approaches are being developed to target IGF2 action. This review provides a clinical perspective on IGF2 and an update on recent research findings.

Maternal–fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer

“…Parent-specific monoallelic expression increased vulnerability to cancer because loss of function of MEGs and reactivation of the silent maternal copy of PEGs would promote cellular proliferation and metastasis. Consistent with these predictions, expression of a cyclin-dependent kinase inhibitor CDKN1C (a MEG) is frequently reduced in cancer [74,75], whereas expression of an insulin-like growth factor IGF2 (a PEG) is frequently increased in cancer [76]. CDKN1C fits the initial predictions for a MEG closely, but not perfectly.…”

The complex genetics of human insulin-like growth factor 2 are not reflected in public databases

“…Similar challenges affecting knowledge of other human genes should promote attempts to critically evaluate, interpret, and correct human genetic data in publicly available databases. ________________________________________ Insulin-like growth factor 2 (IGF2 1 ), a conserved 67-amino acid, single-chain secreted protein, is intimately involved in several critical physiological processes in humans and other mammals (1)(2)(3)(4)(5)(6). IGF2, along with IGF1 and insulin, also comprises a gene family that is found in most mammalian species (7)(8)(9).…”

The role of endocytic Rab GTPases in regulation of growth factor signaling and the migration and invasion of tumor cells

“…57 Insulin growth factor The IGF system is integral to a number of cellular processes ranging from normal growth and development of specific organs, such as in the nervous system, in which IGF signaling regulates neuronal proliferation, apoptosis, and cell survival. [58][59][60] Conversely, IGF also has a critical role in pathological situations, particularly tumorigenesis, and a growing body of epidemiological studies has implicated free IGF-1 serum levels as a risk factor for the development and progression of breast, prostate, colon, and lung cancer. 59,61,62 This adverse effect of IGF is unsurprising given the delicate balance that must be maintained, and the diverse and extensive regulatory function of IGF-1 in maintaining homeostasis.…”