Regulation of Prostate Cancer Dormancy and Recurrence by Hippo Signaling

Abstract

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 YAP/TAZ target genes. Knockdown of the non-coding RNA, SNHG1, induces quiescence, but unexpectedly decreases YAP1 and TAZ mRNA levels, and decreases docetaxel sensitivity. Knockdown of LATS1 or STK3 (MST2) increases quiescence.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2023
Accession Number
AD1212713

Entities

People

  • Frank C Cackowski

Organizations

  • Wayne State University

Tags

Communities of Interest

  • Human Systems

DTIC Thesaurus Topics

  • Bone And Bones
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Genetics
  • Health Services
  • Medical Personnel
  • Oncology
  • Stem Cells

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).