Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition

Kin Wah Lee, Ronnie T.P. Poon, Anthony P. Yuen, Ming Tat Ling, Wei Kei Kwok, Xiang Hong Wang, Yong Chuan Wong, Xinyuan Guan, Kwan Man, King Lok Chau, Sheung Tat Fan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

323 Citations (Scopus)

Abstract

Purpose: Hepatocellular carcinoma (HCC) is a rapidly growing tumor associated with a high propensity for vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, Twist has been identified to play an important role in EMT-mediated metastasis through the regulation of E-cadherin expression. However, the actual role of Twist in tumor invasiveness remains unclear. The purpose of this study is to investigate the expression and possible role of Twist in HCC. Experimental Design: We evaluated Twist and E-cadherin expression in HCC tissue microarray of paired primary and metastatic HCC by immunohistochemical staining. The role of Twist in EMT-mediated invasiveness was also evaluated in vitro in HCC cell lines. Results: We first showed that overexpression of Twist was correlated with HCC metastasis (P = 0.001) and its expression was negatively correlated with E-cadherin expression (P = 0.001, r = -0.443) by tissue microarray. A significant increase of Twist at the mRNA level was also found in metastatic HCC cell lines MHCC-97H, MHCC-97L, and H2M when compared with nonmetastatic Huh-7, H2P, and PLC cell lines. The MHCC-97H cell line, which has a higher metastatic ability, was found to have a higher level of Twist than MHCC-97L. Accompanied with increased Twist expression in the metastatic HCC cell lines when compared with the nonmetastatic primary ones, we found decreased E-cadherin mRNA expression in the metastatic HCC cell lines. By ectopic transfection of Twist into PLC cells, Twist was able to suppress E-cadherin expression and induce EMT changes, which was correlated with increased HCC cell invasiveness. Conclusion: This study shows that Twist overexpression was correlated with HCC metastasis through induction of EMT changes and HCC cell invasiveness.
Original languageEnglish
Pages (from-to)5369-5376
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number18
DOIs
Publication statusPublished - 15 Sep 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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