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Open Access Highly Accessed Research article

Twist expression promotes migration and invasion in hepatocellular carcinoma

Noriyuki Matsuo1, Hidenori Shiraha1*, Tatsuya Fujikawa1, Nobuyuki Takaoka1, Naoki Ueda1, Shigetomi Tanaka1, Shinichi Nishina1, Yutaka Nakanishi1, Masayuki Uemura1, Akinobu Takaki1, Shinichiro Nakamura1, Yoshiyuki Kobayashi1, Kazuhiro Nouso1, Takahito Yagi2 and Kazuhide Yamamoto1

Author Affiliations

1 Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

2 Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

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BMC Cancer 2009, 9:240  doi:10.1186/1471-2407-9-240

Published: 18 July 2009

Abstract

Background

Twist, a transcription factor of the basic helix-loop-helix class, is reported to regulate cancer metastasis. It is known to induce epithelial-mesenchymal transition (EMT). In this study, we evaluated the expression of twist and its effect on cell migration in hepatocellular carcinoma (HCC).

Methods

We examined twist expression using immunohistochemistry in 20 tissue samples of hepatocellular carcinoma, and assessed twist expression in HCC cell lines by RT-PCR and Western blot analysis. Ectopic twist expression was created by introducing a twist construct in the twist-negative HCC cell lines. Endogenous twist expression was blocked by twist siRNA in the twist-positive HCC cell lines. We studied EMT related markers, E-cadherin, Vimentin, and N-cadherin by Western blot analysis. Cell proliferation was measured by MTT assay, and cell migration was measured by in vitro wound healing assay. We used immunofluorescent vinculin staining to visualize focal adhesion.

Results

We detected strong and intermediate twist expression in 7 of 20 tumor samples, and no significant twist expression was found in the tumor-free resection margins. In addition, we detected twist expression in HLE, HLF, and SK-Hep1 cells, but not in PLC/RPF/5, HepG2, and Huh7 cells. Ectopic twist-expressing cells demonstrated enhanced cell motility, but twist expression did not affect cell proliferation. Twist expression induced epithelial-mesenchymal transition together with related morphologic changes. Focal adhesion contact was reduced significantly in ectopic twist-expressing cells. Twist-siRNA-treated HLE, HLF, and SK-Hep1 cells demonstrated a reduction in cell migration by 50, 40 and 18%, respectively.

Conclusion

Twist induces migratory effect on hepatocellular carcinoma by causing epithelial-mesenchymal transition.