Authors
Zheyu Ai, Hao Zhou, Lijuan Jiang, Yuejiao Lang, Zihao Feng, Ziran Dai, Haoqian Feng, Zhenwei Li, Hansen Lin, Jun Lu, Gaowei Huang, Jinchen Luo, Jinhuan Wei, Wei Chen, Junhang Luo, Jingwei He, Anze Yu, Xiaohan Jin, Zhenhua Chen
Published in
Cell reports. Volume 45. Issue 7. Pages 117692. Jul 15, 2026. Epub Jul 15, 2026.
Abstract
Resistance to cisplatin-based chemotherapy remains a major barrier to effective systemic treatment of bladder cancer, underscoring the need for predictive biomarkers and therapeutic targets. Here, we identify YAP1-K90la as a functional post-translational modification that causally drives cisplatin resistance. Across multi-center clinical cohorts, elevated YAP1-K90la levels were associated with poor therapeutic outcomes and outperformed total YAP1 expression in predicting cisplatin responsiveness. Mechanistically, YAP1-K90la enhances YAP1 nuclear localization and transcriptional activity to induce a FOSL1-dependent program that suppresses ferroptosis and promotes cell survival under cisplatin stress. Notably, AARS1 and SIRT1 function as the "writer" and "eraser" of YAP1-K90la, respectively, with SMURF2-mediated ubiquitination of SIRT1 stabilizing YAP1-K90la and driving resistance. Targeting YAP1-K90la using a cell-penetrating peptide restored ferroptotic vulnerability and sensitized bladder cancer cells to cisplatin. Collectively, these findings reveal the YAP1-K90la/FOSL1 pathway that drives cisplatin resistance and position YAP1-K90la as a clinically actionable biomarker and therapeutic target in bladder cancer.
PMID:
42455680
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 4
- Comments 0