Cross-talk and modulation of signaling between somatostatin and growth factor receptors

Abstract

The process of homo- and/or heterodimerization of G-protein coupled receptors (GPCRs) and receptor tyrosine kinase (RTK) families are crucial for implicating the fundamental properties of receptor proteins including receptor expression, trafficking, and desensitization as well as signal transduction. The members of GPCR and RTK family constitute largest cell surface receptor proteins and regulate physiological functions of cells in response to external and internal stimuli. Notably, GPCRs and RTKs play major role in regulation of several key cellular functions which are associated with several pathological conditions including cancer biology, neurodegenerative and cardiovascular diseases. The focus of this review is to highlight the recent findings on the possible cross-talk between somatostatin receptors (members of GPCR family) and growth factor receptors like epidermal growth factor receptors (members of RTK family). Furthermore, functional consequences of such an interaction in modulation of signaling pathways linked to pathological conditions specifically in cancer are discussed.

Human somatostatin receptor-3 distinctively induces apoptosis in MCF-7 and cell cycle arrest in MDA-MB-231 breast cancer cells

“…inhibitory barrier by downregulating SSTRs, which are known to inhibit cell proliferation (Kumar, 2011, Berns et al, 2007. SSTRs are perceived to act as endogenous tumor suppressors and the prominent receptor subtypes associated with apoptosis include SSTR2 and SSTR3 (He et al, 2009, Sharma et al, 1996, Acunzo et al, 2008, Vernejoul et al, 2002, Guillermet et al, 2003, Bousquet et al, 2006, Ferrante et al, 2006.…”

“…There is an inverse relationship between growth factor receptors and SSTR subtypes, which is characterized by gradual loss of SSTRs upon tumor progression and consequent failure of SST analogs mediated antiproliferation (Kumar, 2011). Tumor cells with overexpression of SSTR3 display significantly low proliferation when compared to non-transfected cells and significant inhibition of EGF induced cell proliferation in the presence of SSTR3-specific agonist.…”

“…Previous studies have shown that downregulation of PI3K represents a key step in the development of potential therapeutic targets in tumor of different origin (Kumar, 2011, Altomare and Testa, 2005, Berns et al, 2007, Hynes and Dey, 2009. Interestingly, recent studies have demonstrated a role for SSTRs in the inhibition of PI3K pathway in insulinoma, pituitary and pancreatic tumors (Bousquet et al, 2006, Theodoropoulou et al, 2006, Grozinsky-Glasberg et al, 2008, Kharmate et al, 2011a, Kharmate et al, 2011b.…”

Interrogating Tumor Metabolism and Tumor Microenvironments Using Molecular Positron Emission Tomography Imaging. Theranostic Approaches to Improve Therapeutics

“…GPCRs are one of the largest receptor proteins family (Kumar, 2011), and their discovery earned Robert Lefkowitz and Brian Kobilka the 2012 Nobel Prize in Chemistry. Cross-talk between GPCR and growth factor receptors has a role in downstream signaling activation of proteins that are implicated in cancer growth, angiogenesis, and metastasis (Lappano and Maggiolini, 2011).…”

“…Cross-talk between GPCR and growth factor receptors has a role in downstream signaling activation of proteins that are implicated in cancer growth, angiogenesis, and metastasis (Lappano and Maggiolini, 2011). Dimerization of GPCR is receptor ligand dependent and is not always a necessary mechanism in GPCR activation (Kumar, 2011).…”