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CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

BACKGROUND: 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 ce...

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Autores principales: Huang, Deng, Cao, Li, Zheng, Shuguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240199/
https://www.ncbi.nlm.nih.gov/pubmed/28093067
http://dx.doi.org/10.1186/s13046-016-0474-0
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author Huang, Deng
Cao, Li
Zheng, Shuguo
author_facet Huang, Deng
Cao, Li
Zheng, Shuguo
author_sort Huang, Deng
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-52401992017-01-19 CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma Huang, Deng Cao, Li Zheng, Shuguo J Exp Clin Cancer Res Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2017-01-16 /pmc/articles/PMC5240199/ /pubmed/28093067 http://dx.doi.org/10.1186/s13046-016-0474-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Huang, Deng
Cao, Li
Zheng, Shuguo
CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
title CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
title_full CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
title_fullStr CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
title_full_unstemmed CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
title_short CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
title_sort capza1 modulates emt by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240199/
https://www.ncbi.nlm.nih.gov/pubmed/28093067
http://dx.doi.org/10.1186/s13046-016-0474-0
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