Regulation of Prostate Cancer Dormancy and Recurrence by Hippo Signaling
[Technical Report, Annual Report]
Wayne State University
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In prostate cancer patients with disease apparently localized to the prostate, cancer cells can spread early in the disease process, lie dormant in distant sites and then grow decades after a patient was thought to be cured. In the application for this proposal, we hypothesized that inhibition of hippo signaling or YAP1 and TAZ activation stimulates dormancy escape in prostate cancer. We proposed to Aim 1 Determine which hippo pathway components stimulate or inhibit dormancy escape in vivo, Aim 2 Delineate how tissue mechanics regulate prostate cancer dormancy through the hippo pathway, and Aim 3 Investigate how non-coding RNAs regulate prostate cancer dormancy through the hippo pathway. Thus far, we have found that culture of prostate cancer cells on medium stiffness matrix induces maximal cell cycle activity and transcription of YAPTAZ target genes. Knockdown of the non-coding RNA, SNHG1, induces quiescence, but unexpectedly decreases YAP1 and TAZ mRNA levels. We have also have institutional approval for our animal protocol and have created stable cell lines.
- Medicine and Medical Research