# Crosstalk between YAP1 and Polycomb Group Protein SCML2 in Prostate Cancer

> **NIH NIH U54** · CLARK ATLANTA UNIVERSITY · 2024 · $196,350

## Abstract

PROJECT SUMMARY
PROJECT 3
Prostate cancer with a metastatic castration-resistant phenotype is a leading cause of cancer-related
deaths among men in the United States and worldwide, affecting African Americans disproportionately. The
cellular and molecular mechanisms that contribute to this deadly disease remain poorly understood,
obstructing the development of an effective therapy that prolongs patients’ survival while preserving the
quality of life. The primary goal of this research will be to uncover the mechanism of molecular and functional
interactions between the transcriptional regulatory protein YAP1 and SCML2, a subunit of the Polycomb
repressive complex 1, and to demonstrate that YAP1 and SCML2 cooperate to contribute to invasive
prostate cancer. Using mass spectroscopy-based proteomic approaches, we have identified SCML2 as a
binding partner of the nuclear YAP1 protein complexes from prostate cancer cell lines. Our data showed that
androgen hormone signaling regulates YAP1 and SCML2 interaction in castration-sensitive and castration-
resistant cell lines. Our studies also showed that silencing SCML2 in castration-sensitive cells resulted in
androgen-independent cell growth and led to enzalutamide resistance. However, silencing SCML2 in
castration-resistant cells had the opposite effect when exposed to androgen. In addition, our data showed that
castration-resistant cells express significantly elevated SCML2 compared to castration-sensitive prostate
cancer cells, and the SCML2 gene amplification could contribute to advanced disease. These
observations support the overarching hypothesis that SCML2 and YAP1 cooperate to contribute to invasive
prostate cancer. The primary objectives of this study are to uncover the mechanism of biochemical and
functional interactions between the Hippo pathway effector YAP1 and Polycomb group protein SCML2 in
prostate cancer cells (Aim 1) to determine how altered-SCML2 activity changes the growth behaviors of
prostate tumor cell ex vivo and in vivo (Aim 2), and to evaluate the pattern of SCML2 expression in
prostate cancer disparity tissues and correlated the results with the clinical progression of prostate cancer and
race (Aim 3). This study will provide critical mechanistic insights into the functional and molecular interactions
between the YAP1 and SCML2 regulating cell migration and metastasis. Thus, uncovering a new
mechanism of the aggressive disease may benefit patient care through improved disease surveillance
and targeted selection of patients for more effective targeted therapy, which may reduce disparities in prostate
cancer mortality among men from African American communities. Lastly, YAP1 and SCML2 play a critical
role in the biology of many cancers with poor outcomes, and therefore, knowledge gained through this
research can benefit other cancers with poorer outcomes.

## Key facts

- **NIH application ID:** 10800520
- **Project number:** 2U54MD007590-37
- **Recipient organization:** CLARK ATLANTA UNIVERSITY
- **Principal Investigator:** BEKIR CINAR
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,350
- **Award type:** 2
- **Project period:** 1997-06-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800520

## Citation

> US National Institutes of Health, RePORTER application 10800520, Crosstalk between YAP1 and Polycomb Group Protein SCML2 in Prostate Cancer (2U54MD007590-37). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10800520. Licensed CC0.

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