Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 1549 views | HTML 2241 views | ?
Yuan Liu1, Yong Xu1, Hongxin Ma1, Bo Wang1, Leiqi Xu1, Hualin Zhang1, Xiaojia Song1, Lifen Gao1, Xiaohong Liang1, Chunhong Ma1
1Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, 250012 P.R. China
Xiaohong Liang, e-mail: [email protected]
Chunhong Ma, e-mail: [email protected]
Keywords: HCC, HBx, PPM1a, TGF-β, tumorigenenesis
Received: September 22, 2015 Accepted: April 02, 2016 Published: April 21, 2016
Over-activation of transforming growth factor-β (TGF-β) signaling pathway promotes cell migration and invasion in hepatocellular carcinoma (HCC). The Hepatitis B virus X protein (HBx) is involved in the enhancement of TGF-β signaling pathway in HCC while the mechanism remains unclear. Protein phosphatase magnesium dependent 1A (PPM1a) functions as a phosphatase essential for terminating the TGF-β signaling pathway by dephosphorylating p-Smad2/3. In this study, we found that HBx dose-dependently downregulated PPM1a protein level in the presence of TGF-β, while having no effect on its mRNA level. Further study showed that HBx increased the ubiquitination of PPM1a and accelerated its proteasomal degradation. Restoration of PPM1a almost completely abrogated HBx mediated promotion on HCC migration and invasion. This involvement of PPM1a in HBx-related HCC was further confirmed with immunohistochemical analysis in HCC tissue. Compared with paired pericarcinous tissue, HCC tissue showed decreased PPM1a level. Besides, PPM1a level is negatively correlated with HBx expression. Taken together, our present study suggests that HBx-induced degradation of PPM1a is a novel mechanism for over-activation of TGF-β pathway in HCC development, which might provide potential candidates for clinical diagnosis and treatment.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.