Nature Communications (Apr 2019)
A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis
- Yilong Zou,
- Michael J. Palte,
- Amy A. Deik,
- Haoxin Li,
- John K. Eaton,
- Wenyu Wang,
- Yuen-Yi Tseng,
- Rebecca Deasy,
- Maria Kost-Alimova,
- Vlado Dančík,
- Elizaveta S. Leshchiner,
- Vasanthi S. Viswanathan,
- Sabina Signoretti,
- Toni K. Choueiri,
- Jesse S. Boehm,
- Bridget K. Wagner,
- John G. Doench,
- Clary B. Clish,
- Paul A. Clemons,
- Stuart L. Schreiber
Affiliations
- Yilong Zou
- The Broad Institute
- Michael J. Palte
- The Broad Institute
- Amy A. Deik
- The Broad Institute
- Haoxin Li
- The Broad Institute
- John K. Eaton
- The Broad Institute
- Wenyu Wang
- The Broad Institute
- Yuen-Yi Tseng
- The Broad Institute
- Rebecca Deasy
- The Broad Institute
- Maria Kost-Alimova
- The Broad Institute
- Vlado Dančík
- The Broad Institute
- Elizaveta S. Leshchiner
- The Broad Institute
- Vasanthi S. Viswanathan
- The Broad Institute
- Sabina Signoretti
- Department of Oncologic Pathology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School
- Toni K. Choueiri
- Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School
- Jesse S. Boehm
- The Broad Institute
- Bridget K. Wagner
- The Broad Institute
- John G. Doench
- The Broad Institute
- Clary B. Clish
- The Broad Institute
- Paul A. Clemons
- The Broad Institute
- Stuart L. Schreiber
- The Broad Institute
- DOI
- https://doi.org/10.1038/s41467-019-09277-9
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 13
Abstract
Clear-cell carcinomas are aggressive tumours characterised by high accumulation of lipids and glycogen. Here, the authors report that these cancers have a common vulnerability to GPX4 inhibition-induced ferroptosis and using CRISPR screen and lipodomic profiling, they identify HIF-2α- HILPDA axis promotes ferroptosis via enrichment of PUFA lipids.
