# Regulation of prostate epithelial basal cell plasticity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2024 · $321,365

## Abstract

Project Summary
 Prostatitis is a common urinary tract problem for men. Although pathological and epidemiological
studies have linked prostatitis to the development of prostate cancer, its molecular mechanism remains
unclear. Answering this question will have clinical benefits in prostate cancer prevention and early intervention.
It has been proposed that inflammation can induce tissue stem cell expansion, thereby enlarging the cellular
pool for oncogenic transformation. In the prostate, epithelial basal cells serve as stem cells during
organogenesis and injury repair, but are quiescent in adult homeostasis. Preliminary data in mouse models
suggest that prostatitis reactivates adult basal cells to promote basal-to-luminal differentiation, which facilitates
the initiation and progression of prostate cancer. The goal of this project is to elucidate the mechanisms
regulating basal cell plasticity in prostatitis and apply the knowledge for prostate cancer prevention. Our central
hypothesis is that dysregulation of the androgen receptor (AR) and Wnt signaling crosstalk through an increase
of Wnt/β-catenin activity and insufficient AR sequestration is a major factor underlying basal cell reactivation in
prostatitis. In three specific aims, we will use an integrated approach of mouse genetics, in vivo lineage tracing,
prostate organoid culture, ChIP-seq, biochemistry, single cell RNA-seq, and bioinformatics to determine the AR
and β-catenin cistromes in basal cells in prostatitis, characterize the inflammatory stromal environment
essential for the enhancement of basal Wnt activities, and assess the effectiveness of Wnt inhibition in
delaying prostatitis-stimulated cancer. This project will provide novel insights into the mechanistic link between
prostatitis and prostate cancer, a long-standing question in the field. The research outcomes will positively
impact human health since Wnt signaling is a druggable target and its inhibition is a potentially promising
treatment for ameliorating prostatitis-induced cancer progression.

## Key facts

- **NIH application ID:** 10795669
- **Project number:** 5R01CA271452-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Zhu Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $321,365
- **Award type:** 5
- **Project period:** 2015-09-25 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795669

## Citation

> US National Institutes of Health, RePORTER application 10795669, Regulation of prostate epithelial basal cell plasticity (5R01CA271452-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10795669. Licensed CC0.

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