The IGF-II–Insulin Receptor Isoform-A Autocrine Signal in Cancer: Actionable Perspectives

Cancers

Pierluigi Scalia¹  StephenJ. Williams¹  Antonio Giordano¹ 

[1] Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, Biology Department, Temple University, Philadelphia, PA 19122, USA;

关键词: igf(i/ii/1r), insulin-like growth factor (1 or 2 or receptor);    ir^a/ir-a;    insulin receptor isoform a;    igfbp;    igf binding protein;    itn;    integrin;    m6pr;    mannose 6 phosphate receptor;    tf;    transferrin;    vtn;    vitronectin;    hif;    hypoxia-inducible factor;    vhl;    von hippel-lindau gene product;    oct;    off-context targeting;   

DOI  :  10.3390/cancers12020366

来源: DOAJ

【 摘 要 】

Insulin receptor overexpression is a common event in human cancer. Its overexpression is associated with a relative increase in the expression of its isoform A (IR^A), a shorter variant lacking 11 aa in the extracellular domain, conferring high affinity for the binding of IGF-II along with added intracellular signaling specificity for this ligand. Since IGF-II is secreted by the vast majority of malignant solid cancers, where it establishes autocrine stimuli, the co-expression of IGF-II and IR^A in cancer provides specific advantages such as apoptosis escape, growth, and proliferation to those cancers bearing such a co-expression pattern. However, little is known about the exact role of this autocrine ligand−receptor system in sustaining cancer malignant features such as angiogenesis, invasion, and metastasis. The recent finding that the overexpression of angiogenic receptor kinase EphB4 along with VEGF-A is tightly dependent on the IGF-II/IR^A autocrine system independently of IGFIR provided new perspectives for all malignant IGF2omas (those aggressive solid cancers secreting IGF-II). The present review provides an updated view of the IGF system in cancer, focusing on the biology of the autocrine IGF-II/IR^A ligand−receptor axis and supporting its underscored role as a malignant-switch checkpoint target.

【 授权许可】

Unknown