The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer
cystine transporter and transsulfuration pathway enzymes CBS and CTH to increase intracellular cysteine levels, enabling anti-ferroptotic glutathione production. HIF-2 also induces the Parkin mitophagy factor and suppresses mitochondrial function and reactive oxygen species (ROS) generation. Altogether, our findings uncover an unforeseen role of the HIF-2 transcription factor as a coordinator of anti-ferroptotic mechanisms in pancreatic cancer.
Authors
- Maimon E. Hubbi (ORCID: https://orcid.org/0000-0001-9763-287X)
- Yasir Suhail (ORCID: https://orcid.org/0000-0002-1296-9738)
- Erin E. Hollander
- Ben Z. Stanger (ORCID: https://orcid.org/0000-0003-0410-4037)
- Chi V. Dang
- Jane Xie
- Nadia L. Almasri
- Kshitiz
- Alexander Muir
- Catherine L. Wang
Institutions
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- University of Chicago (US)
- UPMC Hillman Cancer Center (US)
- Ludwig Cancer Research (US)
- UConn Health (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Molecular Cell
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1016/j.molcel.2026.03.007
- Citations
- 1
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 21.88
Funders
- Ludwig Institute for Cancer Research
- Pancreatic Cancer Research Fund
- National Institutes of Health