Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis Journal Article
| Authors: | Xie, Y.; Liu, S.; Lu, W.; Yang, Q.; Williams, K. D.; Binhazim, A. A.; Carver, B. S.; Matusik, R. J.; Chen, Z. |
| Article Title: | Slug regulates E-cadherin repression via p19Arf in prostate tumorigenesis |
| 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. |
| Keywords: | immunohistochemistry; nonhuman; animal cell; mouse; animal tissue; animal experiment; animal model; genotype; protein p53; uvomorulin; cancer model; carcinogenesis; prostate cancer; cancer cell; western blotting; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; tissue microarray; cyclin dependent kinase inhibitor; transcription factor slug; short hairpin rna; slug; mouse model; epithelial mesenchymal transition; sumo 1 protein; male; article; sumo1 |
| Journal Title: | Molecular Oncology |
| Volume: | 8 |
| Issue: | 7 |
| ISSN: | 1878-0261 |
| Publisher: | FEBS Press |
| Date Published: | 2014-10-01 |
| Start Page: | 1355 |
| End Page: | 1364 |
| Language: | English |
| DOI: | 10.1016/j.molonc.2014.05.006 |
| PROVIDER: | scopus |
| PMCID: | PMC4198473 |
| PUBMED: | 24910389 |
| DOI/URL: | |
| Notes: | Export Date: 1 December 2014 -- Source: Scopus |
