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Actin‐like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial‐mesenchymal transition
Author(s) -
Xiao Shuai,
Chang RuiMin,
Yang MingYang,
Lei Xiong,
Liu Xiao,
Gao WenBin,
Xiao JingLei,
Yang LianYue
Publication year - 2016
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28417
Subject(s) - epithelial–mesenchymal transition , cancer research , metastasis , sox2 , ectopic expression , gene knockdown , hepatocellular carcinoma , cell migration , notch signaling pathway , biology , hccs , carcinogenesis , cancer , signal transduction , medicine , cell , cell culture , transcription factor , microbiology and biotechnology , gene , biochemistry , genetics
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide because of metastasis. Epithelial‐mesenchymal transition (EMT) is widely considered to be crucial to the invasion‐metastasis cascade during cancer progression. Actin‐like 6A (ACTL6A) is initially verified important for cell proliferation, differentiation, and migration. In this study, we find that ACTL6A plays an essential role in metastasis and EMT of HCC. ACTL6A expression is up‐regulated in HCC cells and tissues. A high level of ACTL6A in HCCs is correlated with aggressive clinicopathological features and is an independent poor prognostic factor for overall and disease‐free survival of HCC patients. Ectopic expression of ACTL6A markedly promotes HCC cells migration, invasion, as well as EMT in vitro and promotes tumor growth and metastasis in the mouse xenograft model. Opposite results are observed when ACTL6A is knocked down. Mechanistically, ACTL6A promotes metastasis and EMT through activating Notch signaling. ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N‐[N‐(3,5‐difluorophenacetyl)‐L‐alanyl]‐S‐phenylglycine t‐butylester, in HCC cells. Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)‐box 2 (SOX2) expression and then activate Notch1 signaling. Conclusions : ACTL6A promotes metastasis and EMT by SOX2/Notch1 signaling, indicating a prognostic biomarker candidate and a potential therapeutic target for HCC. (H epatology 2016;63:1256–1271)