Loss of BPTF restores estrogen response and suppresses metastasis of mammary tumors
Context-specific epigenetic dependencies, shaped by chromatin remodeling can create exploitable vulnerabilities for cancer therapies that are unique to tissue types and cellular identities. Here, we show that loss of BPTF (Bromodomain PHD Finger Transcription Factor), a core component of the NURF (Nucleosome Remodeling Factor) complex, results in the emergence of estrogen-responsive, tamoxifen-sensitive, Estrogen Receptor alpha (ERα) positive mammary tumors without altering cancer cell state and tumor pathology. Elevated ERα levels in BPTF<sup>KO</sup> mammary tumor cells are linked with decreased TGF-β activity and limited metastatic spread of mammary tumor cells to the lungs. Loss of ERα is sufficient to restore TGF-β activity and the metastatic potential in BPTF<sup>KO</sup> tumors. These findings highlight a mechanism through which BPTF regulates tumor development and progression in mammary epithelial cells, offering insights into the interplay between chromatin remodeling, estrogen signaling, and their resultant adjuvant therapeutic potential in breast cancer.
Authors
- Dhivyaa Anandan (ORCID: https://orcid.org/0000-0001-8272-8756)
- Deeptiman Chatterjee (ORCID: https://orcid.org/0000-0003-2752-4640)
- Mackenzie K. Callaway (ORCID: https://orcid.org/0000-0002-8102-5466)
- John Erby Wilkinson (ORCID: https://orcid.org/0000-0001-9174-8556)
- Chris Z. Zhao (ORCID: https://orcid.org/0000-0003-1404-0313)
- Camila O. dos Santos (ORCID: https://orcid.org/0000-0002-3999-9523)
- Amritha Varshini Hanasoge Somasundara (ORCID: https://orcid.org/0000-0001-9411-0873)
- William C. K. Pomerantz (ORCID: https://orcid.org/0000-0002-0163-4078)
- Michael F. Ciccone
- Julie Hanson Ostrander (ORCID: https://orcid.org/0000-0002-5038-6875)
- Adam Siepel (ORCID: https://orcid.org/0000-0002-3557-7219)
- Si-jin Yang
- Yixin Zhao (ORCID: https://orcid.org/0000-0002-7856-2818)
- Steven M. Lewis (ORCID: https://orcid.org/0000-0002-1979-0554)
- Jessica Tollkühn (ORCID: https://orcid.org/0000-0001-5991-7620)
- David L. Spector (ORCID: https://orcid.org/0000-0003-3614-4965)
- Marygrace C. Trousdell (ORCID: https://orcid.org/0000-0002-4824-7040)
- Chen Chen (ORCID: https://orcid.org/0000-0001-7075-8501)
- Suzanne Russo
- R. S. Anderson
Institutions
- University of Minnesota (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Washington (US)
- Washington University in St. Louis (US)
- Cold Spring Harbor Laboratory (US)
- Brown University (US)
- University of Minnesota Medical Center (US)
- Sanya University (CN)
- Stony Brook University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-15
- DOI
- https://doi.org/10.1038/s41467-025-64255-8
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00