start-ver=1.4 cd-journal=joma no-vol=9 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2009 dt-pub=20090718 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Twist expression promotes migration and invasion in hepatocellular carcinoma en-subtitle= kn-subtitle= en-abstract= kn-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. en-copyright= kn-copyright= en-aut-name=MatsuoNoriyuki en-aut-sei=Matsuo en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShirahaHidenori en-aut-sei=Shiraha en-aut-mei=Hidenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FujikawaTatsuya en-aut-sei=Fujikawa en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakaokaNobuyuki en-aut-sei=Takaoka en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=UedaNaoki en-aut-sei=Ueda en-aut-mei=Naoki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TanakaShigetomi en-aut-sei=Tanaka en-aut-mei=Shigetomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NishinaShinichi en-aut-sei=Nishina en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanishiYutaka en-aut-sei=Nakanishi en-aut-mei=Yutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UemuraMasayuki en-aut-sei=Uemura en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakakiAkinobu en-aut-sei=Takaki en-aut-mei=Akinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NakamuraShinichiro en-aut-sei=Nakamura en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KobayashiYoshiyuki en-aut-sei=Kobayashi en-aut-mei=Yoshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NousoKazuhiro en-aut-sei=Nouso en-aut-mei=Kazuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=YamamotoKazuhide en-aut-sei=Yamamoto en-aut-mei=Kazuhide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ affil-num=2 en-affil= kn-affil=Okayama Univ affil-num=3 en-affil= kn-affil=Okayama Univ affil-num=4 en-affil= kn-affil=Okayama Univ affil-num=5 en-affil= kn-affil=Okayama Univ affil-num=6 en-affil= kn-affil=Okayama Univ affil-num=7 en-affil= kn-affil=Okayama Univ affil-num=8 en-affil= kn-affil=Okayama Univ affil-num=9 en-affil= kn-affil=Okayama Univ affil-num=10 en-affil= kn-affil=Okayama Univ affil-num=11 en-affil= kn-affil=Okayama Univ affil-num=12 en-affil= kn-affil=Okayama Univ affil-num=13 en-affil= kn-affil=Okayama Univ affil-num=14 en-affil= kn-affil=Okayama Univ affil-num=15 en-affil= kn-affil=Okayama Univ END