Publication Date
1-3-2024
Journal
Communications Biology
DOI
10.1038/s42003-023-05727-9
PMID
38172561
PMCID
PMC10764307
PubMedCentral® Posted Date
1-3-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Male, Humans, Mice, Animals, Cystathionine, Cystathionine beta-Synthase, Cell Proliferation, Prostatic Neoplasms, Heat-Shock Response, Cancer metabolism, Prostate cancer
Abstract
There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell proliferation and reduction of transsulfuration pathway metabolites. Combination of HSF1 and CBS knockout decreases tumor size for a small cell PCa xenograft mouse model. Our study thus provides new insights into the molecular mechanism of HSF1 function and an effective therapeutic strategy against advanced PCa.
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