11 Recent studies indicated that aPKC ι is the sole catalytic component of the Par3-Par6-aPKC ι complex, which has a critical role in the establishment and maintenance of epithelial cell polarity, tight junctions, and adherens junctions. It is an important signaling molecule taking part in transformation, adhesion, movement, invasion, and metastasis of tumor cells. 6, 7, 8 Although several EMT-related transcription factors such as Snail, Twist, and Zinc finger E-box binding protein 1 (ZEB1) have been shown to be involved in the process of EMT in HCC, 9, 10 the molecular mechanisms underlying the regulation of EMT in HCC have not yet been fully elucidated.Ītypical protein kinase C ι (aPKC ι) is a newly discovered aPKC, which is independent of calcium, diacylglycerol, and is only activated by phospholipids. 5 A correlation between the expression profiles of EMT, and tumor recurrence or distant metastasis, has been demonstrated in certain types of cancer, including HCC. The characteristic changes during EMT include the downregulation of epithelial markers, such as E-cadherin and the upregulation of mesenchymal markers such as vimentin. 4 Epithelial–mesenchymal transition (EMT) has been shown to be a pivotal mechanism contributing to cancer invasion and metastasis, as epithelial cells lose their polarity and acquire the migratory properties of mesenchymal cells. 3 However, the risk of 5-year recurrence of HCC following hepatic resection is as high as 50–70%, due to its high invasion and the frequent intra- and/or extra-hepatic metastases. 1, 2 HCC is curable by surgical resection or liver transplantation if diagnosed at early stage. In the last decade, hepatocellular carcinoma (HCC) is considered to be the most lethal of cancers, accounting for approximately one-third of all malignancies. ATM might be a promising agent for targeted treatment of HCC. In conclusion, our result suggested that aPKC ι could be an important bio-marker of tumor EMT, and used as an indicator of invasion and malignancy. However, ATM increased proliferation of epithelial cells and had little effect on apoptosis and invasion of epithelial cells. Moreover, ATM selectively inhibited proliferation of mesenchymal cells and HepG2 cells and induced apoptosis. Furthermore, we showed that the aPKC ι blocking agent aurothiomalate (ATM) inhibited EMT and decreased invasion of hepatocytes. Our study showed that EMT took place in MMH-R cells under the effect of transforming growth factor- β1 (TGF- β1) overexpressing aPKC ι. To explore the regulatory mechanism of atypical protein kinase C ι (aPKC ι) signaling pathways to HCC development, and find an agent for targeted therapy for HCC, immortalized murine hepatocytes were employed to establish an EMT cell model of HCC, MMH-RT cells. Epithelial-to-mesenchymal transition (EMT) has an important role in invasion and metastasis of hepatocellular carcinoma (HCC).
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