Heat shock factor 1 (HSF1) cooperates with estrogen receptor α (ERα) in the regulation of estrogen action in breast cancer cells
Natalia Vydra,
Patryk Janus,
Paweł Kus,
Tomasz Stokowy,
Katarzyna Mrowiec,
Agnieszka Toma-Jonik,
Aleksandra Krzywon,
Alexander Jorge Cortez,
Bartosz Wojtas,
Bartłomiej Gielniewski,
Roman Jaksik,
Marek Kimmel,
Wieslawa Widlak
Affiliations
Natalia Vydra
Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej, Gliwice, Poland
Patryk Janus
Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej, Gliwice, Poland; Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland
Paweł Kus
Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland
Tomasz Stokowy
Department of Clinical Science, University of Bergen, Bergen, Norway
Katarzyna Mrowiec
Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej, Gliwice, Poland
Agnieszka Toma-Jonik
Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeże Armii Krajowej, Gliwice, Poland
Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland; Departments of Statistics and Bioengineering, Rice University, Houston, United States
Heat shock factor 1 (HSF1), a key regulator of transcriptional responses to proteotoxic stress, was linked to estrogen (E2) signaling through estrogen receptor α (ERα). We found that an HSF1 deficiency may decrease ERα level, attenuate the mitogenic action of E2, counteract E2-stimulated cell scattering, and reduce adhesion to collagens and cell motility in ER-positive breast cancer cells. The stimulatory effect of E2 on the transcriptome is largely weaker in HSF1-deficient cells, in part due to the higher basal expression of E2-dependent genes, which correlates with the enhanced binding of unliganded ERα to chromatin in such cells. HSF1 and ERα can cooperate directly in E2-stimulated regulation of transcription, and HSF1 potentiates the action of ERα through a mechanism involving chromatin reorganization. Furthermore, HSF1 deficiency may increase the sensitivity to hormonal therapy (4-hydroxytamoxifen) or CDK4/6 inhibitors (palbociclib). Analyses of data from The Cancer Genome Atlas database indicate that HSF1 increases the transcriptome disparity in ER-positive breast cancer and can enhance the genomic action of ERα. Moreover, only in ER-positive cancers an elevated HSF1 level is associated with metastatic disease.
