Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

19 Scopus Citations
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Author(s)

  • Liang Dong
  • Qi Dong
  • Ying Chen
  • Bao Zhang
  • Xiaoming Lyu
  • George G. Chen
  • Paul Lai
  • Hsiang-fu Kung

Detail(s)

Original languageEnglish
Article number22
Journal / PublicationSignal Transduction and Targeted Therapy
Volume3
Online published24 Aug 2018
Publication statusPublished - 2018

Link(s)

Abstract

Tbx3, a transcriptional repressor, is essential in the organogenesis of vertebrates, stem cell self-renewal and differentiation, and the carcinogenesis of multiple tumor types. However, the mechanism by which Tbx3 participates in the metastasis of hepatocellular carcinoma (HCC) remains largely unknown. In this study, we show that Tbx3 was dramatically upregulated in clinical HCC samples and that elevated expression of Tbx3 promoted cancer progression. To determine the underlying mechanism, systematic glycine scan mutagenesis and deletion assays were performed. We identified two critical motifs, 585LFSYPYT591 and 604HRH606, that contribute to the repression of transcriptional activity. These motifs are also essential for Tbx3 to promote cell migration and metastasis both in vitro and in vivo via the suppression of E-cadherin expression. More importantly, Tbx3 directly interacts with HDAC5 via these motifs, and an HDAC inhibitor blocks Tbx3-mediated cell migration and the downregulation of E-cadherin in HCC. As Tbx3 is involved in the carcinogenesis of multiple types of human cancers, our findings suggest an important target for anti-cancer drug development.

Research Area(s)

Citation Format(s)

Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma. / Dong, Liang; Dong, Qi; Chen, Ying; Li, Yichen; Zhang, Bao; Zhou, Fanghang; Lyu, Xiaoming; Chen, George G.; Lai, Paul; Kung, Hsiang-fu; He, Ming-Liang.

In: Signal Transduction and Targeted Therapy, Vol. 3, 22, 2018.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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