AI Article Synopsis
- - The study emphasizes the need for new treatment targets in prostate cancer to create innovative therapies.
- - Researchers discovered that gambogic acid (GBA) can induce pyroptosis in prostate cancer cells by targeting a previously hard-to-drug protein called CNPY3.
- - GBA's mechanism involves recruiting the enzyme SIRT1, which alters CNPY3 and leads to lysosomal rupture, promoting cell death; this suggests CNPY3 could be a valuable target for future treatments.
Article Abstract
There is an urgent requirement to acquire a comprehensive comprehension of novel therapeutic targets for prostate cancer to facilitate the development of medications with innovative mechanisms. In this study, we identified gambogic acid (GBA) as a specific pyroptosis inducer in prostatic cancer cells. By using a thermal proteome profiling (TPP) strategy, we revealed that GBA induces pyroptosis by directly targeting the canopy FGF signaling regulator (CNPY3), which was previously considered "undruggable". Moreover, through the utilization of the APEX2-based proximity labeling method, we found that GBA recruited delactatease SIRT1, resulting in the elimination of lysine lactylation (Kla) on CNPY3. Of note, SIRT1-mediated delactylation influenced the cellular localization of CNPY3 to promote lysosome rupture for triggering pyroptosis. Taken together, our study identified CNPY3 as a distinctive cellular target for pyroptosis induction and its potential application in prostate cancer therapy.
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| http://dx.doi.org/10.1021/acs.jmedchem.4c00140 | DOI Listing |
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