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Loss of BPTF restores estrogen response and suppresses metastasis of mammary tumors

Author

Listed:
  • Michael F. Ciccone

    (Cold Spring Harbor Laboratory)

  • Dhivyaa Anandan

    (Cold Spring Harbor Laboratory
    Stony Brook University
    Stony Brook University)

  • Deeptiman Chatterjee

    (Cold Spring Harbor Laboratory)

  • Chen Chen

    (Washington University School of Medicine in St. Louis)

  • Marygrace C. Trousdell

    (Brown University)

  • Rebecca Anderson

    (Cold Spring Harbor Laboratory)

  • Steven M. Lewis

    (Cold Spring Harbor Laboratory
    Stony Brook University
    Stony Brook University)

  • Mackenzie K. Callaway

    (Cold Spring Harbor Laboratory)

  • Chris Z. Zhao

    (Cold Spring Harbor Laboratory
    Cold Spring Harbor Laboratory)

  • Amritha Varshini Hanasoge Somasundara

    (Memorial Sloan Kettering Cancer Center)

  • Suzanne Russo

    (Cold Spring Harbor Laboratory)

  • Shih-Ting Yang

    (Cold Spring Harbor Laboratory)

  • Yixin Zhao

    (Yazhouwan National Laboratory)

  • Julie Ostrander

    (University of Minnesota)

  • John E. Wilkinson

    (University of Washington)

  • William C. K. Pomerantz

    (University of Minnesota)

  • Adam Siepel

    (Cold Spring Harbor Laboratory)

  • David L. Spector

    (Cold Spring Harbor Laboratory)

  • Jessica Tollkuhn

    (Cold Spring Harbor Laboratory)

  • Camila O. Santos

    (Cold Spring Harbor Laboratory)

Abstract

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 BPTFKO 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 BPTFKO 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.

Suggested Citation

  • Michael F. Ciccone & Dhivyaa Anandan & Deeptiman Chatterjee & Chen Chen & Marygrace C. Trousdell & Rebecca Anderson & Steven M. Lewis & Mackenzie K. Callaway & Chris Z. Zhao & Amritha Varshini Hanasog, 2025. "Loss of BPTF restores estrogen response and suppresses metastasis of mammary tumors," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64255-8
    DOI: 10.1038/s41467-025-64255-8
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    References listed on IDEAS

    as
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