# Androgen and Wnt signaling in bladder cancer

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $168,960

## Abstract

ABSTRACT
Bladder cancer is the 4th most common cancer in men and 11th in women. Despite that bladder
development and function are not sex hormone-dependent, men are three times more likely to develop
bladder cancer than women. Smoking has been shown not to be a contributor for this gender bias. Instead,
intrinsic sex-differences likely underpin the molecular mechanism for male susceptibility to bladder cancer.
Sex hormones and sex chromosomes are obvious suspects to account for this male predilection for
bladder cancer. In fact, experimental evidence in rodents strongly support a crucial role for androgen
receptor in promoting cancer development in a chemical-induced bladder cancer model. In addition to
androgen signaling, the other undeniably powerful regulator of lower urinary tract development and
carcinogenesis is the WNT signaling pathway. β-catenin is the signal integrator of canonical WNT signaling
and AR and β-catenin physically interact to synergistically activate transcription. This interaction is crucial
for downstream target expression during genital masculinization, bladder cancer development and
progression. Despite the crucial roles these two pathways play in bladder carcinogenesis, their direct
transcriptional targets, which are likely drivers of bladder cancer initiation, remain elusive. In this
application, we propose to use a recently developed powerful technology, Split DamID to reveal in vivo
transcriptional targets downstream of AR, p300 and β-catenin during bladder cancer development. In Aim
1, we will use our newly generated transgenic model to reveal direct AR and p300 transcriptional targets in
a carcinogen-induced bladder cancer model. Next, in Aim 2, we will use SpDamID on bladder organoids to
reveal AR and β-catenin direct targets, followed by siRNA functional screen for their roles in promoting
organoid formation. Together, these studies should greatly improve our understanding of bladder cancer
initiation, especially those controlled by AR and Wnt signaling.

## Key facts

- **NIH application ID:** 10850812
- **Project number:** 5R21CA283677-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Liang Ma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $168,960
- **Award type:** 5
- **Project period:** 2023-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850812

## Citation

> US National Institutes of Health, RePORTER application 10850812, Androgen and Wnt signaling in bladder cancer (5R21CA283677-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10850812. Licensed CC0.

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