Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis

Yingqiu Xie, Shenji Liu, Wenfu Lu, Qing Yang, Kieosha D. Williams, Awadh A. Binhazim, Brett S. Carver, Robert J. Matusik, Zhenbang Chen

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

SLUG represses E-cadherin to promote epithelial-mesenchymal transition (EMT) in various cancers. Mechanisms that regulate SLUG/E-cadherin pathway remain poorly understood, especially during tumorigenesis invivo. Here we report that p19Arf (p14ARF in human) stabilizes Slug to inhibit E-cadherin in prostate cancer mouse models. Inactivation of p19Arf reduces Slug levels, resulting in increased E-cadherin expression and delaying the onset and progression of prostate cancer in Pten/Trp53 double null mice. Mechanistically, p14ARF stabilizes SLUG through increased sumoylation at lysine residue 192. Importantly, levels of SLUG and p14ARF are positively correlated in human prostate cancer specimens. These data demonstrated that ARF modulates the SLUG/E-cadherin signaling axis for augmenting prostate tumorigenesis invivo, revealing a novel paradigm where the oncogenic functions of SLUG require ARF to target E-cadherin in prostate cancer. Collectively, our findings further support that ARF has dual tumor suppressive/oncogenic roles in cancers in a context-dependent manner.

Original languageEnglish
Pages (from-to)1355-1364
Number of pages10
JournalMolecular Oncology
Volume8
Issue number7
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Mouse model
  • Prostate cancer
  • SLUG
  • SUMO1

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Medicine
  • Medicine(all)

Fingerprint Dive into the research topics of 'Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis'. Together they form a unique fingerprint.

  • Cite this

    Xie, Y., Liu, S., Lu, W., Yang, Q., Williams, K. D., Binhazim, A. A., Carver, B. S., Matusik, R. J., & Chen, Z. (2014). Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis. Molecular Oncology, 8(7), 1355-1364. https://doi.org/10.1016/j.molonc.2014.05.006