Somatostatin and Epidermal Growth Factor Receptors: Implications in Breast Cancer

Ujendra Kumar, Geetanjali Kharmate


Despite several advances, the underlying mechanism of complexity of breast cancer progression still remains elusive. In addition to the genetic predisposition, several growth factor receptors including insulin growth factor receptor (IGF), platelet derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) relaying proliferative signals are accountable for disease progression. Epidermal growth factor receptors (EGFRs, or commonly known as ErbBs), members of the receptor tyrosine kinase family (RTKs), play a central role in tumor growth, progression and metastatic disease. Typically, agonist dependent activation of EGFR results in receptor phosphorylation, homo- and/or heterodimerization and modulation of signaling pathways leading to cell proliferation, survival and metastasis. Targeting one or multiple steps in EGFR-mediated tumor progression may serve as a better approach in drug therapies. Unlike EGFRs, G-protein coupled somatostatin receptors (SSTRs) have been recognized as negative regulators of breast tumors. The activation of SSTRs modulates downstream signaling responsible for tumor growth and consequent cytostatic or cytotoxic effects on tumor proliferation. SSTR subtypes are well characterized to form homo-and/or heterodimers within the same family as well as with other GPCRs. Clinically, the chimeric molecule targeting both SSTR5 and dopamine receptors (specifically dopamine receptor 2) is in use for the treatment of pituitary tumors. This review describes the interplay between SSTRs and EGFR and the potential role of such cross talk in attenuation of EGFR-mediated signaling pathways involved in tumorigenesis. Furthermore, recent findings supporting the role of SSTR in EGFR-mediated signaling in tumor biology are discussed in detail.


Breast Cancer, Dimerization, Heterodimerization, Epidermal growth factor, Epidermal growth factor Receptors, Somatostatin, Somatostatin Receptors


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