The APKCι Blocking Agent ATM Negatively Regulates EMT And Invasion Of Hepatocellular Carcinoma

Purpose:To investigate the function and regulatory mechanism of aPKCl signaling pathways in epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC). Furthermore, to find an agent for targeted therapy for HCC.Methods:The TGF-β1worked with constitutively active v-Ha-Ras to establish a hepatocellular carcinoma EMT cell model (MMH-RT cells) by lentivirus infection. The expression of aPKCl and EMT markers were measured by Western Blot which were utilized to analyse the correlationship between the expression of aPKCl with EMT of hepatocellular carcinoma. The aPKCt blocking agent aurothiomalate (ATM) was indentified in the MMH-RT hepatocytes. The transwell assay and FACS were used to investigate the invasive and apotosis changes during the treatment by ATM.Results:Our study showed that EMT took place in MMH-R cells under the effect of TGF-β1over-expressing aPKCl. Furthermore, we showed that the aPKCl blocking agent aurothiomalate (ATM) inhibited EMT and decreased invasion of hepatocytes. Moreover, ATM selectively inhibited proliferation of mesenchymal cells and HepG2cells and induced apoptosis. However, ATM increased proliferation of epithelial cells and had little effect on apoptosis and invasion of epithelial cells.Conclusion:In conclusion, our result suggested that aPKCl could be an important bio-marker of tumor EMT, and used as an indicator of invasion and malignancy. ATM might be a promising agent for targeted treatment of HCC.