Paxillin mediates extranuclear and intranuclear signaling in prostate cancer proliferation
Aritro Sen1, Ismary De Castro, Donald B Defranco
1Division of Endocrinology and Metabolism, University of Rochester Medical Center, Rochester, NY, USA.
The Journal of Clinical Investigation
|June 12, 2012
Summary
Paxillin, a protein, acts as a crucial link in prostate cancer cell signaling. It regulates both androgen- and growth factor-driven proliferation, suggesting it as a therapeutic target for prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Prostate cancer proliferation signals shift from castration-sensitive to castration-resistant states.
- Understanding shared signaling components is key for effective prostate cancer treatment strategies.
Purpose of the Study:
- To investigate the role of paxillin in regulating prostate cancer cell proliferation.
- To identify paxillin as a potential therapeutic target and biomarker for prostate cancer.
Main Methods:
- Studied paxillin's function in androgen- and EGF-induced signaling pathways.
- Utilized human prostate cancer cell xenografts and tissue microarrays to assess paxillin's expression and requirement for tumor growth.
Main Results:
- Paxillin mediates MAPK-dependent nuclear translocation in response to androgens and EGF.
- Nuclear paxillin interacts with the androgen receptor (AR) and transcription factors (ERK, ELK1) to regulate AR-mediated transcription and gene expression (c-FOS, cyclin D1).
- Paxillin is essential for prostate cancer cell xenograft growth and is upregulated in human prostate cancer tissues.
Conclusions:
- Paxillin acts as a critical liaison between extranuclear signaling and nuclear transcription in prostate cancer.
- Paxillin is a potential biomarker for prostate cancer proliferation and a promising therapeutic target.
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