This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, T. K. Articles by Fan, S. T. Search for Related Content PubMed PubMed Citation Articles by Lee, T. K. Articles by Fan, S. T.

Twist Overexpression Correlates with Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition

Authors' Affiliations: ¹ Centre for the Study of Liver Disease, and Departments of ² Surgery, ³ Anatomy, and ⁴ Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, China

Requests for reprints: Ronnie T.P. Poon, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong. Phone: 852-2855-3641; Fax: 852-2817-5475; E-mail: poontp{at}hkucc.hku.hk.

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.

This article has been cited by other articles:

				L. Hu, J. M. Roth, P. Brooks, S. Ibrahim, and S. Karpatkin Twist Is Required for Thrombin-Induced Tumor Angiogenesis and Growth Cancer Res., June 1, 2008; 68(11): 4296 - 4302. [Abstract] [Full Text] [PDF]

				G. Z. Cheng, W. Zhang, M. Sun, Q. Wang, D. Coppola, M. Mansour, L. Xu, C. Costanzo, J. Q. Cheng, and L.-H. Wang Twist Is Transcriptionally Induced by Activation of STAT3 and Mediates STAT3 Oncogenic Function J. Biol. Chem., May 23, 2008; 283(21): 14665 - 14673. [Abstract] [Full Text] [PDF]

				W. K. Kwok, M.-T. Ling, H. F. Yuen, Y.-C. Wong, and X. Wang Role of p14ARF in TWIST-mediated senescence in prostate epithelial cells Carcinogenesis, December 1, 2007; 28(12): 2467 - 2475. [Abstract] [Full Text] [PDF]

				H.-W. Lo, S.-C. Hsu, W. Xia, X. Cao, J.-Y. Shih, Y. Wei, J. L. Abbruzzese, G. N. Hortobagyi, and M.-C. Hung Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-regulation of TWIST Gene Expression Cancer Res., October 1, 2007; 67(19): 9066 - 9076. [Abstract] [Full Text] [PDF]

				T. Horikawa, J. Yang, S. Kondo, T. Yoshizaki, I. Joab, M. Furukawa, and J. S. Pagano Twist and Epithelial-Mesenchymal Transition Are Induced by the EBV Oncoprotein Latent Membrane Protein 1 and Are Associated with Metastatic Nasopharyngeal Carcinoma Cancer Res., March 1, 2007; 67(5): 1970 - 1978. [Abstract] [Full Text] [PDF]