MTBP inhibits migration and metastasis of hepatocellular carcinoma

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• 作者：Qian Bi (1) (2) (3)
  Atul Ranjan (2)
  Rui Fan (3)
  Neeraj Agarwal (2)
  Danny R. Welch (2)
  Steven A. Weinman (4)
  Jie Ding (3)
  Tomoo Iwakuma (2)
  
  1. Diagnosis and Treatment Center for Liver Cirrhosis ; 302 Military Hospital of China ; Beijing ; 10039 ; People鈥檚 Republic of China
  2. Department of Cancer Biology ; The University of Kansas Cancer Center ; 3901 Rainbow Blvd ; Kansas City ; KS ; 66010 ; USA
  3. State Key Laboratory of Cancer Biology ; Xijing Hospital of Digestive Diseases ; Fourth Military Medical University ; Xi鈥檃n ; 710032 ; People鈥檚 Republic of China
  4. Department of Internal Medicine ; University of Kansas Medical Center ; Kansas City ; KS ; 66010 ; USA
  
• 关键词：Hepatocellular carcinoma ; MTBP ; ACTN4 ; Migration ; Metastasis
• 刊名：Clinical & Experimental Metastasis
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：32
• 期：4
• 页码：301-311
• 全文大小：4,437 KB
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• 刊物主题：Cancer Research; Biomedicine general; Oncology; Hematology; Surgical Oncology;
• 出版者：Springer Netherlands
• ISSN：1573-7276

文摘

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with increasing incidence. Despite curative surgical resection and advanced chemotherapy, its survival rate remains low. The presence of microvascular invasion and occult metastasis is one of the major causes for this poor outcome. MDM2 Binding Protein (MTBP) has been implicated in the suppression of cell migration and cancer metastasis. However, clinical significance of MTBP, particularly in human cancer, is poorly understood. Specifically, clinical relevance of MTBP in human HCC has never been investigated. Here we demonstrated that expression of MTBP was significantly reduced in human HCC tissues compared to adjacent non-tumor tissues. MTBP expression was negatively correlated with capsular/vascular invasion and lymph node metastasis. Overexpression of MTBP resulted in the suppression of the migratory and metastatic potential of HCC cells, while its downregulation increased the migration. Consistent with the previous report, MTBP endogenously bound to alpha-actinin 4 (ACTN4) and suppressed ACTN4-mediated cell migration in multiple HCC cell lines. However, MTBP also inhibited migratory potential of PLC/PRF/5 HCC cells whose migration was not altered by manipulation of ACTN4 expression. These results suggest that mechanisms behind MTBP-mediated migration suppression may not be limited to the pathway involving ACTN4 in certain cellular contexts. Additionally, as a potential mechanism for reduced MTBP expression in tumors, we found that MTBP expression was increased following the treatment with histone deacetylase inhibitors (HDIs). Our study, for the first time, provides clinical relevance of MTBP in the suppression of HCC metastasis.