title: Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.
abstract: 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.
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Rui-Min
authors.initials: RM
authors.lastname: Chang
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Yang
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Lei
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Gao
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Xiao
authors.affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Lian-Yue
authors.initials: LY
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000235:genetics*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D011897:Random Allocation; D016019:Survival Analysis; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C116160:ACTL6A protein, human; D000199:Actins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins