MAPK signalling pathway: Role in cancer pathogenesis

Abstract

Cancer is one of the prime causes of death presently. In normal cells, the firmly regulated pathway relays extracellular signals from the cell membrane to nucleus through a cascade of phosphorylation events. The Mitogen-Activated Protein Kinase (MAPK) cascades are among the most thoroughly studied signal transduction systems and have been proven to participate in a diverse array of cellular programs consisting of cell differentiation, cell movement, cell division and cell death. Constitutive activation of the MAPK cascade is associated with the carcinogenesis and melanoma development because of activating mutations within the B-RAF and RAS genes or other genetic or epigenetic modifications in their components or upstream activation of cell-surface receptors (e. g., EGFR and Flt-3) and chimeric chromosomal translocations (e. g. BCR-ABL) leading to elevated signaling activity eliciting cellular proliferation, invasion, metastasis, migration, survival and angiogenesis. Even in the absence of apparent genetic mutations, MAPK pathway has been stated to be activated in over 50% of Acute Myelogenous Leukemia (AML) and acute lymphocytic leukemia. In this brief review, we are about to outline the current advances in understanding the regulation of Mitogen-activated protein kinase signaling system and how can we generate specificity.