The Role of the Insulin Receptor Isoforms in the Insulin- Like Growth Factor Signaling Axis in Cancer

Brianne L Sanford and Dawn S Chandler

Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children’s Hospital, USA
Department of Pediatrics, The Ohio State University, USA

^*Correspondance to: Dawn S Chandler 

 PDF  Full Text Mini Review | Open Access

Abstract:

The Insulin-like Growth Factor (IGF) signaling system is known for regulating critical cellular processes related to growth and apoptosis. The IGF-axis is activated upon IGF stimulation of the IGF-1 receptor (IGF-1R), and it has been well demonstrated that increased expression of IGF-1R and the IGF-2 ligand is implicated in cell transformation and tumor propagation. For several decades, efforts have been focused on developing treatment strategies aimed at inhibiting IGF-1R action but produced suboptimal results. Recent research has confirmed the presence of an autocrine signaling loop involving IGF-2 and an insulin receptor isoform A (IR-A), which is produced as a result of alternative splicing of the IR. Stimulation of full-length IR (IR-B) by insulin typically activates glucose regulating pathways, whereas IR-A activation by IGF-2 leads to mitogenic signaling. IR-A is a naturally occurring isoform, prevalent during fetal development and in certain tissues. It is also shown to be highly upregulated in many cancer types, increasing the cancer cell’s responsiveness to IGF-2 thus providing the tumor cell a growth advantage. In this mini review, we discuss the mechanism of IR alternative splicing and its role in cancer and treatment resistance.

Keywords:

Cancer; IGF-2; Insulin receptor; Insulin-like growth factor-1 receptor; Splicing

Cite the Article:

Sanford BL, Chandler DS. The Role of the Insulin Receptor Isoforms in the Insulin-Like Growth Factor Signaling Axis in Cancer. Clin Oncol. 2017; 2: 1236.