Related Experiment Video
Updated: Apr 26, 2026
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Crosstalk between nuclear MET and SOX9/β-catenin correlates with castration-resistant prostate cancer
Yingqiu Xie1, Wenfu Lu, Shenji Liu
1Department of Biochemistry and Cancer Biology (Y.X., W.L., S.L., Q.Y., Z.C.), Meharry Medical College, Nashville, Tennessee 37208; Department of Surgery and Division of Urology (B.S.C.), Memorial Sloan-Kettering Cancer Center, New York, New York 10065; and Vancouver Prostate Centre and Department of Urologic Sciences (E.L., Y.W., L.F., M.G.), The University of British Columbia, Vancouver, British Columbia, Canada V6H 3Z6.
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.
Insights
Nuclear MET is crucial for castration-resistant prostate cancer (CRPC) recurrence. Elevated nuclear MET drives cancer cell reprogramming and proliferation, offering a new therapeutic target for recurrent prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Castration-resistant prostate cancer (CRPC) poses a significant mortality risk.
- Mechanisms driving CRPC relapse after androgen ablation therapy remain poorly understood.
Purpose of the Study:
- To investigate the role of the nuclear form of mesenchymal epithelial transition factor (nMET) in CRPC.
- To elucidate the molecular pathways through which nMET contributes to CRPC progression.
Main Methods:
- Analysis of human CRPC and naïve prostate cancer samples.
- In vitro studies on androgen-nonresponsive PCa cells under androgen deprivation.
- In vivo studies using a Pten/Trp53 null mouse model of recurrent prostate cancer.
Main Results:
- Nuclear MET (nMET) is significantly increased in human CRPC samples.
- Androgen deprivation induces nMET, promoting PCa cell proliferation and stem-like properties.
- nMET activates SOX9, β-catenin, and Nanog, driving sphere formation.
- MET accumulates in the nucleus in recurrent tumors, contrasting with membrane localization in naïve tumors.
Conclusions:
- nMET plays an essential role in CRPC development and recurrence.
- The nMET-SOX9/β-catenin axis drives cell reprogramming and cancer recurrence.
- Targeting nMET presents a promising new therapeutic strategy for recurrent prostate cancer.
Related Concept Videos
01:23Catenins
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
01:33Pleiotropy