AR activates YAP/TAZ differentially in prostate cancer
Omar Salem1,2, Siyang Jia1,2, Bin-Zhi Qian3
1The University of Edinburgh, Centre for Inflammation Research, Edinburgh BioQuarter, Edinburgh, UK.
Life Science Alliance
|June 29, 2023
Summary
Androgens activate YAP/TAZ via the androgen receptor (AR) in prostate cancer, influencing cell growth. Targeting YAP/TAZ or SRF sensitizes cancer cells to AR inhibition, offering new therapeutic strategies.
Area of Science:
- Cell Biology
- Oncology
- Molecular Biology
Background:
- The Hippo signaling pathway regulates cell growth and is implicated in cancer.
- YAP and TAZ are key transcriptional co-regulators of the Hippo pathway, playing roles in various cancers.
- The precise mechanisms of YAP/TAZ activation in most cancers remain unclear.
Purpose of the Study:
- To investigate how androgens activate YAP/TAZ through the androgen receptor (AR) in prostate cancer.
- To elucidate the regulatory mechanisms of AR-mediated YAP/TAZ activation.
- To explore the therapeutic potential of targeting YAP/TAZ and SRF in prostate cancer.
Main Methods:
- Investigated androgen-mediated activation of YAP/TAZ via AR in prostate cancer cells.
- Analyzed AR's regulation of YAP translation and TAZ transcription (WWTR1).
- Examined the role of serum response factor (SRF) in AR-mediated YAP/TAZ activation and correlated SRF expression with YAP/TAZ target genes in patient data.
Main Results:
- Androgens activate YAP/TAZ via AR in prostate cancer, with differential regulation of YAP and TAZ.
- AR regulates YAP translation and induces TAZ (WWTR1) transcription.
- AR-mediated YAP/TAZ activation is controlled by SRF, and SRF expression correlates with TAZ and YAP/TAZ target genes (CYR61, CTGF) in prostate cancer patients.
- YAP/TAZ are not essential for AR activity but targeting them or SRF sensitizes prostate cancer cells to AR inhibition under anchorage-independent growth conditions.
Conclusions:
- Dissected the cellular roles of YAP, TAZ, and SRF in prostate cancer.
- Highlighted the interplay between YAP, TAZ, and SRF in prostate tumorigenesis.
- Suggested therapeutic strategies targeting YAP/TAZ or SRF to enhance AR inhibition efficacy in prostate cancer.
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