Loss of BPTF restores estrogen response and suppresses metastasis of mammary tumors.
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 Hanasoge Somasundara, Suzanne Russo, Shih-Ting Yang, Yixin Zhao, Julie Ostrander, John E Wilkinson
Abstract
Open AccessContext-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.