title: CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma.
abstract: Epithelial-mesenchymal transition (EMT) elicits dramatic changes, including cytoskeleton remodelling as well as changes in gene expression and cellular phenotypes. During this process, actin filament assembly plays an important role in maintaining the morphology and movement of tumour cells. Capping protein, a protein complex referred to as CapZ, is an actin-binding complex that can regulate actin cytoskeleton remodelling. CAPZA1 is the α1 subunit of this complex, and we hypothesized that CAPZA1 regulates EMT through the regulation of actin filaments assembly, thus reducing the metastatic ability of hepatocellular carcinoma (HCC) cells.
  
  
  
  Immunohistochemistry was used to detect CAPZA1 expression in 129 HCC tissues. Western blotting and qPCR were used to detect CAPZA1, EMT markers and EMT transcription factors in HCC cells. Transwell migration and invasion assays were performed to observe the migration and invasion of HCC cells. Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of HCC cells. Immunoprecipitation was used to detect the interaction between CAPZA1 and actin filaments. Finally, a small animal magnetic resonance imager (MRI) was used to observe metastases in HCC cell xenografts in the liver.
  
  
  
  CAPZA1 expression levels were negatively correlated with the biological characteristics of primary HCC and patient prognosis. CAPZA1 expression was negatively correlated with the migration and invasion of HCC cells. CAPZA1 down regulation promoted the migration and invasion of HCC cells. Conversely, CAPZA1 overexpression significantly inhibited the migration and invasion of HCC cells. Moreover, CAPZA1 expression levels were correlated with the expression of the EMT markers E-cadherin, N-cadherin and Vimentin. Furthermore, the expression of Snail1 and ZEB1 were negatively correlated with CAPZA1 expression levels. Similarly, CAPZA1 significantly inhibited intrahepatic metastases of HCC cells in an orthotopic transplantation tumour model.
  
  
  
  CAPZA1 inhibits EMT in HCC cells by regulating actin cytoskeleton remodelling, thereby reducing the metastatic ability of the cells. Together, our data suggest that CAPZA1 could be a useful biomarker for clinical determination of the prognosis of HCC patients.
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, No.29 Gaotanyan Road, Shapingba District, Chongqing, 400038, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Huang
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, No.29 Gaotanyan Road, Shapingba District, Chongqing, 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, No.29 Gaotanyan Road, Shapingba District, Chongqing, 400038, China. shuguozh@163.com.
authors.forename: Shuguo
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D000818:Animals; D051347:CapZ Actin Capping Protein / Q000235:genetics* / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011379:Prognosis
chemical_list: D000199:Actins; C495842:CAPZA1 protein, human; D051347:CapZ Actin Capping Protein
keywords: Actin; CAPZA1; Epithelial-mesenchymal transition (EMT); Metastasis; Primary hepatocellular carcinoma (HCC)