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Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition via Akt/GSK-3β/snail signaling.
|Title||Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition via Akt/GSK-3β/snail signaling.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Liu L, Dai Y, Chen J, Zeng T, Li Y, Chen L, Zhu Y-H, Li J, Li Y, Xie D, Yuan Y-F, Guan X-Y|
|Journal||Hepatology (Baltimore, Md.)|
|Date Published||2013 Aug 8|
Amplification of 1q is one of the most frequent chromosomal alterations in human hepatocellular carcinoma (HCC). In this study, we have identified and characterized a novel oncogene, Maelstrom (MAEL), at 1q24. Amplification and overexpression of MAEL was frequently detected in HCCs and significantly associated with HCC recurrence (P=0.031) and poor outcome (P=0.004). Functional study demonstrated that MAEL promoted cell growth, cell migration and tumor formation in nude mice, all of which were effectively inhibited when MAEL was silenced with shRNAs. Further study found that MAEL enhanced AKT activity with subsequent GSK-3β phosphorylation and Snail stabilization, finally inducing epithelial-mesenchymal transition (EMT) and promoting tumor invasion and metastasis. In addition, MAEL upregulated various stemness-related genes, multidrug resistance genes and cancer stem cell (CSC) surface markers at the mRNA level. Functional study demonstrated that overexpression of MAEL increased self-renewal, chemoresistance and tumor metastasis. Taken together, we have shown MAEL to be a novel oncogene that plays an important role in the development and progression of HCC by inducing EMT and enhancing the stemness of HCC. (Hepatology 2013;).