Slug Regulates E-cadherin Repression Via P19Arf in Prostate Tumorigenesis

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2014 Jun 10

PMID 24910389

Citations 35

Authors

Yingqiu Xie

Shenji Liu

Wenfu Lu

Qing Yang

Kieosha D Williams

Awadh A Binhazim

Brett S Carver

Robert J Matusik

Zhenbang Chen

Affiliations

Soon will be listed here.

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 in vivo. Here we report that p19(Arf) (p14(ARF) in human) stabilizes Slug to inhibit E-cadherin in prostate cancer mouse models. Inactivation of p19(Arf) 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, p14(ARF) stabilizes SLUG through increased sumoylation at lysine residue 192. Importantly, levels of SLUG and p14(ARF) are positively correlated in human prostate cancer specimens. These data demonstrated that ARF modulates the SLUG/E-cadherin signaling axis for augmenting prostate tumorigenesis in vivo, 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.

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