CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma
| العنوان: | CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma |
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| المؤلفون: | Shuguo Zheng, Li Cao, Deng Huang |
| المصدر: | Journal of Experimental & Clinical Cancer Research : CR |
| بيانات النشر: | BioMed Central, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Cancer Research, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Cell, Vimentin, Metastasis, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, Cell Movement, Cell Line, Tumor, Gene expression, medicine, Animals, Humans, Neoplasm Metastasis, Cytoskeleton, Actin, Cell Proliferation, CapZ Actin Capping Protein, biology, CAPZA1, Research, Liver Neoplasms, CapZ, Hep G2 Cells, Middle Aged, Actin cytoskeleton, Prognosis, digestive system diseases, Actins, Cell biology, Epithelial-mesenchymal transition (EMT), 030104 developmental biology, medicine.anatomical_structure, Oncology, Primary hepatocellular carcinoma (HCC), 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female, Neoplasm Transplantation |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1756-9966 0392-9078 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8053c709734facc2a5d682489fc93a1Test http://europepmc.org/articles/PMC5240199Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a8053c709734facc2a5d682489fc93a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17569966 03929078 |
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