Critical role of DEK and its regulation in tumorigenesis and metastasis of hepatocellular carcinoma

Le Yu, Xiaobin Huang, Wenfa Zhang, Huakan Zhao, Gang Wu, Fenglin Lv, Lei Shi, Yong Teng

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally. Therefore, it is quite essential to identify novel HCC-related molecules for the discovery of new prognostic markers and therapeutic targets. As an oncogene, DEK plays an important role in cell processes and participates in a variety of cellular metabolic functions, and its altered expression is associated with several human malignancies. However, the functional significance of DEK and the involved complex biological events in HCC development and progression are poorly understood. Here, combing the results from clinical specimens and cultured cell lines, we uncover a critical oncogenic role of DEK, which is highly expressed in HCC cells. DEK protein encompasses two isoforms (isoforms 1 and 2) and isoform 1 is the most frequently expressed DEK isoform in HCC cells. DEK depletion by using shRNA inhibited the cell proliferation and migration in vitro and suppressed tumorigenesis and metastasis in mouse models. Consistently, DEK overexpression regardless of which isoform produced the opposite effects. Further studies showed that DEK induced cell proliferation through upregulating cell cycle related CDK signaling, and promoted cell migration and EMT, at least in part, through the repression of β-catenin/E-cadherin axis. Interestingly, isoform 1 induced cell proliferation more efficiently than isoform 2, however, no functional differences existed between these two isoforms in cell migration. Together, our study indicates that DEK expression is required for tumorigenesis and metastasis of HCC, providing molecular insights for DEK-related pathogenesis and a basis for developing new strategies against HCC.

Original languageEnglish (US)
Pages (from-to)26844-26855
Number of pages12
JournalOncotarget
Volume7
Issue number18
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

  • DEK
  • HCC
  • Isoform
  • Metastasis
  • Migration

ASJC Scopus subject areas

  • Oncology

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