Research
XPO5 regulates ferroptosis via MITF-ACSL4 signaling to drive CRPC progression and serves as a druggable target
Cell Reports Medicine · By Mengmeng Wang, Shuangwei Liu, Lei Xu, Weiteng Cao, Xinyue Wang, Yubo Wang, Yanshuo Cheng, Ning Liu, Ziqi Huang, Kun Zhang, Ranlu Liu, Lan Ma, Cheng Yang & Guang Yang ·
The Brief
- Study by Wang et al. reports that XPO5 promotes castration-resistant prostate cancer (CRPC) progression by suppressing ferroptosis via the MITF-ACSL4 axis.
- The authors identify an XPO5-targeting molecular glue degrader that induces ferroptosis in cellular, CDX and PDX models.
- The findings are preclinical and the authors describe XPO5 as a potential druggable target.
Why it matters
It identifies a mechanistic link between a nuclear export protein, ferroptosis suppression and CRPC progression, and tests a degrader in several tumour models, which could guide future drug development. Results remain preclinical.
Who’s affected
- prostate cancer researchers
- drug discovery scientists working on ferroptosis or targeted protein degradation
- #prostate cancer
- #ferroptosis
- #xpo5
- #protein degradation
- #drug target
Wang et al. show that XPO5 drives CRPC progression by suppressing ferroptosis through the MITF-ACSL4 axis. They identify an XPO5-targeting molecular glue degrader that induces ferroptosis in cellular, CDX, and PDX models, supporting its translational potential.
Timeline
Study published in Cell Reports Medicine
cell.com
XPO5 regulates ferroptosis via MITF-ACSL4 signaling to drive CRPC progression and serves as a druggable target