Targeting Certain Molecular Interactions Could Yield New Strategies for Treating Prostate Cancer

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10/09/2023

Contact: Steven Lee, (210) 450-3823, lees22@uthscsa.edu

SAN ANTONIO, Oct. 5, 2023 – Research led by Mays Cancer Center at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) has discovered that altering certain molecular interactions could yield new strategies for treating prostate cancer and related diseases.

The study focuses on androgen receptors (AR), which are protein molecules that help direct the development of male sexual characteristics, essentially by turning genes on or off as necessary.

The researchers determined that an optimum level of androgen receptor “multivalent interactions” likely is required for proper function. Multivalent interactions involve a simultaneous binding of multiple molecules on the same regulatory chromatin sites to control gene expression. (Chromatin refers to a mixture of DNA and proteins that form the chromosomes found in cells.) The scientists also concluded that alterations of these interactions might underlie the cause and development of disease.

Zhijie “Jason” Liu, PhD

“Our results provide molecular insights for potential therapeutic strategies to treat prostate cancer and other AR-involved diseases by targeting AR multivalent interactions,” said Zhijie “Jason” Liu, PhD, associate professor and CPRIT Scholar in Cancer Research with Mays Cancer Center and the Institute of Biotechnology of the Department of Molecular Medicine at UT Health San Antonio.

He is lead author of the article titled, “Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions,” published Sept. 21 in Molecular Cell, a journal of research in molecular biology. Other researchers are from the Sam and Ann Barshop Institute for Longevity and Aging Studies at UT Health San Antonio; the California Institute of Technology; and the Duke Cancer Institute at Duke University.

They observed that androgen receptors form local high-concentration “condensates” – membrane-less subunits that carry out specialized cell functions – through protein-clustering interactions. These are driven by certain multivalent interactions in response to androgen hormone stimulation.

The researchers determined that disturbing those condensates impairs androgen receptor function in the assembly of “enhancers,” referring to DNA sequences that activate transcription independently.

“Our work using AR as an example provides evidence for the importance of maintaining precise levels of multivalent interactions to achieve beneficial hormone-induced enhancer assembly events,” Liu said. “Collectively, our results suggest that disruption of the fine-tuned AR protein multivalent interactions might underlie AR-related human pathologies.

“AR multivalent interactions,” he concluded, “could be pharmacologically targeted to treat prostate cancer and other AR-involved diseases.”


Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions

Lizhen Chen, Zhao Zhang, Qinyu Han, Barun K. Maity, Leticia Rodrigues, Emily Zbori, Rashmi Adhikari, Su-Hyuk Ko, Xin Li, Shawn R. Yoshida, Pengya Xue, Emilie Smith, Kexin Xu, Qianben Wang, Tim Hui-Ming Huang, Shasha Chong, Zhijie Liu

First published: Sept. 21, 2023, Molecular Cell

Link to article: Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions: Molecular Cell


The University of Texas Health Science Center at San Antonio (UT Health San Antonio) is one of the country’s leading health science universities and is designated as a Hispanic-Serving Institution by the U.S. Department of Education. With missions of teaching, research, patient care and community engagement, its schools of medicine, nursing, dentistry, health professions, graduate biomedical sciences and public health have graduated more than 42,200 alumni who are leading change, advancing their fields and renewing hope for patients and their families throughout South Texas and the world. To learn about the many ways “We make lives better®,” visit UTHealthSA.org.

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The Mays Cancer Center at UT Health San Antonio is one of only four National Cancer Institute-designated Cancer Centers in Texas. The Mays Cancer Center provides leading-edge cancer care, propels innovative cancer research and educates the next generation of leaders to end cancer in South Texas. To learn more, visit https://cancer.uthscsa.edu.

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