Studies of Erk1/2 with Respect to Tumor Aggressiveness in B16f10 Murine Melanoma Cells

Abstract

Melanoma is a very aggressive form of skin cancer and have the potential to spread from a small sized primary tumor and metastasizes to different locations like lungs, bones, lymph nodes, liver and even brain. Extracellular signal regulated kinase (ERK) molecule present in MAPK pathway plays a major role in different carcinogenic processes like cell migration, cell invasiveness by altering the extracellular matrix (ECM). Cell invasiveness is facilitated by matrix metalloproteins (MMPs) by means of degradation of gelatinase enzyme regulated by a family of receptor proteins called integrins. ECM ligand fibronectin causes increased secretion of MMPs, specially MMP2 and MMP9 facilitating invasiveness and metastasis in cancer cells. This study aims to find the modulatory role of ERK 1/ 2 with respect to tumor aggressiveness on both MMP2 and MMP9 on melanoma metastasis and invasion. ERK pathway was downregulated through administration of inhibitors and ERK 1/ 2 siRNA gene silencing the effect on MMP2 and MMP9 was studied. The studies were done in B16F10 melanoma cell line and mice model. Significant changes were found in levels of MMP2 and MMP9 after downregulating the ERK pathway and can therefore a correlation between ERK and MMP activities was concluded. Elucidating these molecular phenomena in melanoma, this result can help in developing and improving targeted cancer therapies with multiple options in drug discovery.