Preliminary Studies On The Mechanism Of C-Abl Kinase Acting In MMP-2Mediated Melanoma Cell Migration

Tumor metastasis is the major reason for cancer patients death. Melanoma is onekind of the high metastatic tumors. The metastatic process includes angiogenesis,extracellular matrix remodeling, cell migration, and immunologic escape. While all stepspromote the tumor invasion and metastasis, the remodeling of extracellular matrix bytumors and adjacent tissues is pivotal to the success of metastasis, during which, manykinds of proteases acting cooperatively, especially MMPs, play a prominent role inmelanoma. c-Abl is one kind of tyrosine kinases and presents high expression level intumor cells acting in proliferation, survival, migration and adhesion, and can directlybind with actin cytoskeleton.This article focuses on the mechanism of c-Abl kinase acting in melanoma cell lineA375invasion mediated by MMP-2. Preliminary studies on the role of c-Abl in MMP-2expression, secretion and activation has been done.The results demonstrate that c-Ablkinase has no effect on MMP-2expression, but can promote the secreting of MMP-2, andrestrain the activation of proMMP-2. At the same time, we use co-immunoprecipitationto explore the interaction between MMP-2and integrin αvβ3,and the results show thatc-Abl kinase keeps the location of MMP-2on the cell surface through binding withintegrin αvβ3， further promoting extracellular matrix transformation in direction.Moreover, we detect the effection of c-Abl kinase on invadopodium formation byimmunofluorescence.The results demonstrate that c-Abl promotes invadopodiumsformation and inhibits focal adhesion assembly, integrally accelerating A375invasion.The conclusion is that c-Abl kinase plays a key role in A375invasion through severalprocesses.The finding of this research establishes a theoretical foundation for the further andsystemic understanding of c-Abl kinase function in A375invasion and also builts a targetfor anti-cancer agents.