Crosstalk between nuclear MET and SOX9/β-catenin correlates with castration-resistant prostate cancer Journal Article
| Authors: | Xie, Y.; Lu, W.; Liu, S.; Yang, Q.; Carver, B. S.; Li, E.; Wang, Y.; Fazli, L.; Gleave, M.; Chen, Z. |
| Article Title: | Crosstalk between nuclear MET and SOX9/β-catenin correlates with castration-resistant prostate cancer |
| Abstract: | Castration-resistant prostate cancer (PCa) (CRPC) is relapse after various forms of androgen ablation therapy and causes a major mortality in PCa patients, yet the mechanism remains poorly understood. Here, we report the nuclear form of mesenchymal epithelial transition factor (nMET) is essential for CRPC. Specifically, nMET is remarkably increased in human CRPC samples compared with naïve samples. Androgen deprivation induces endogenous nMET and promotes cell proliferation and stem-like cell self-renewal in androgen-nonresponsive PCa cells. Mechanistically, nMET activates SRY (sex determining region Y)-box9, β-catenin, and Nanog homeobox and promotes sphere formation in the absence of androgen stimulus. Combined treatment of MET and β-catenin enhances the inhibition of PCa cell growth. Importantly, MET accumulation is detected in nucleus of recurrent prostate tumors of castrated Pten/Trp53 null mice, whereas MET elevation is predominantly found in membrane of naïve tumors. Our findings reveal for the first time an essential role of nMET association with SOX9/β-catenin in CRPC in vitro and in vivo, highlighting that nuclear RTK activate cell reprogramming to drive recurrence, and targeting nMET would be a new avenue to treat recurrent cancers. |
| Keywords: | controlled study; human tissue; unclassified drug; human cell; androgen; cancer recurrence; nonhuman; protein function; cell proliferation; animal cell; mouse; animal tissue; protein protein interaction; animal experiment; animal model; cell renewal; in vivo study; in vitro study; carcinogenesis; cancer inhibition; infant; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; cell membrane; cell nucleus; cancer tissue; antiandrogen; beta catenin; concentration response; transcription factor nanog; nuclear reprogramming; scatter factor receptor; castration resistant prostate cancer; protein aggregation; transcription factor sox9; human; male; article; prostate cancer cell line; nuclear mesenchymal epithelial transition factor |
| Journal Title: | Molecular Endocrinology |
| Volume: | 28 |
| Issue: | 10 |
| ISSN: | 0888-8809 |
| Publisher: | Endocrine Society |
| Date Published: | 2014-10-01 |
| Start Page: | 1629 |
| End Page: | 1639 |
| Language: | English |
| DOI: | 10.1210/me.2014-1078 |
| PROVIDER: | scopus |
| PMCID: | PMC4179634 |
| PUBMED: | 25099011 |
| DOI/URL: | |
| Notes: | Export Date: 3 November 2014 -- Source: Scopus |
