Osteopontin promotes epithelial-mesenchymal transition of hepatocellular carcinoma through regulating vimentin
| Autor: | Yuan-Yuan Sheng, Jian Yu, Chun Dai, Qiongzhu Dong, Peng Qiao, Yi Qin, Xiao-Fei Zhang, Hai-Jun Zhou, Qing-Hai Ye, Ning Ren, Lu Xie, Jinwang Wei, Hu-Liang Jia, Xu-Chao Zhu, Chuang Zhou, Xin-Xin Yu, Lun-Xiu Qin, Xiao-Mei Gao, Yan Zheng |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine osteopontin Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Mice Nude Vimentin Kaplan-Meier Estimate Protein degradation Metastasis Mice 03 medical and health sciences vimentin stomatognathic system Cell Line Tumor Biomarkers Tumor medicine Animals Humans Epithelial–mesenchymal transition Osteopontin Aged Gene knockdown biology Protein Stability Liver Neoplasms hepatocellular carcinoma stability Middle Aged Prognosis medicine.disease digestive system diseases 030104 developmental biology Oncology Hepatocellular carcinoma Cancer cell biology.protein Cancer research Heterografts Female Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Our previous studies have found that osteopontin (OPN) is a promoter for hepatocellular carcinoma (HCC) progression. However, the molecular mechanism by which OPN enhances HCC metastasis remains elusive. Epithelial-mesenchymal transition (EMT) of cancer cells plays a pivotal role in promoting metastatic process. In this study, we demonstrated that OPN promotes HCC metastasis by inducing an EMT-like, more aggressive cellular phenotype in vitro and in vivo. Furthermore, OPN was identified to interact with vimentin by reciprocal OPN and vimentin immunoprecipitation as well as co-immunofluorescence examination. By using deletion mutants, we found that the residues between 246 and 406 in vimentin are required for binding to OPN. Importantly, OPN significantly increased vimentin stability through inhibition of its protein degradation. Knockdown of vimentin neutralized the EMT induced by OPN both in vitro and in vivo. Moreover, a significant correlation between OPN and vimentin levels was found in clinical HCC specimens and their combination had a worse prognosis with shorter overall survival (OS) and time to recurrence (TTR). In multivariate analysis, OPN and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Collectively, this study indicates that OPN can induce EMT of HCC cells through increasing vimentin stability, which provides more in-depth understanding about the molecular mechanisms of OPN in promoting HCC metastasis and opens tantalizing therapeutic possibilities in HCC. |
| Databáze: | OpenAIRE |
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