DAB2IP regulates EMT and metastasis of prostate cancer through targeting PROX1 transcription and destabilizing HIF1α protein

Bin Wang, Jun Huang, Jiancheng Zhou, Ke Hui, Shan Xu, Jinhai Fan, Lei Li, Xinyang Wang, Jer Tsong Hsieh, Dalin He, Kaijie Wu

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Prospero-related homeobox 1 (PROX1) is an essential regulator in lymphangiogenesis and has been implicated in both oncogenic and tumor-suppressive functions in many types of human cancers. However, the role of PROX1 in prostate cancer (PCa) remains poorly understood. In this study, based on different PCa cell lines and knockout mice, we showed that PROX1 could be suppressed by DAB2IP, a novel member of the Ras GTPase-activating protein family and a critical player in control of epithelial-mesenchymal transition (EMT) and PCa metastasis. Mechanistically, PROX1 overexpression in DAB2IP-deficient PCa cells could enhance the accumulation of HIF1α protein by inhibiting ubiquitin pathway and then consequently induce an EMT response, which is characterized by repression of E-cadherin, up-regulation of vimentin and matrix metallopeptidases (MMPs) and enhancement of cell migration. Together, our data provides a new insight into mechanism that DAB2IP regulates EMT and PCa metastasis, especially points out the potential roles of its downstream PROX1/HIF1α signaling in a unique non-skeletal metastasis of PCa.

Original languageEnglish (US)
Pages (from-to)1623-1630
Number of pages8
JournalCellular Signalling
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2016

Keywords

  • DAB2IP
  • EMT
  • HIF1α
  • Metastasis
  • Prostate cancer
  • PROX1

ASJC Scopus subject areas

  • Cell Biology

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