Importance of PKB/Akt/mTOR signalling pathway in motility of hepatocelluler carcinoma cells

Liver cancer is the fifth most frequent cancer and the third cause of tumor-related death in the world. Hepatocellular carcinoma (HCC) is a very agressive tumor . Its incidence is %83 among the liver cancers. PI3K/Akt/mTOR signalling pathway controls proliferation, apoptosis and autophagy of the cells. Moreover this pathway has a role in HCC occurance and development. Cells adhere the extracellular matrix (ECM) by their integrins and this adhesion stimulates PI3K/Akt/mTOR signalling pathway. The importance of PI3K signalling on cell motility in HCC cells has not been well established.In our experiments we used three different cell lines (Huh7, SNU449, MV) which have different activated Akt levels. We studied the effect of LY294002, which is the specific inhibitor of PI3K, on cell motility in the presence of ECM components. In order to examined the effect of LY294002 on cell motility, we used wound healing assay and motility/invasion chambers. Furthermore Reverse-Transcriptase polymerase chain reaction was performed to determine in three HCC cell lines.ECM components increase cell motility in these three cell lines. LY294002 has an opposite effect on cell motility. It has observed that expression profilles of beta 4, alfa 1, alfa 2 and alpha 4 integrins have changed as in time and presence of collagen I dependent manner.Our result indicate that the presence of collagen I might increase integrin alpha 1 expression by activating PI3K signalling pathway in HCC cell lines studied .Key words: Hepatocellular Carcinoma, PI3K/AKT/mTOR signalling pathway, extrasellular matrix, integrin