Browsing by Author "Toma-Jonik, Agnieszka"

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    Heat shock factor 1 (HSF1) cooperates with estrogen receptor α (ERα) in the regulation of estrogen action in breast cancer cells
    (eLife Sciences Publications Ltd, 2021) Vydra, Natalia; Janus, Patryk; Kus, Paweł; Stokowy, Tomasz; Mrowiec, Katarzyna; Toma-Jonik, Agnieszka; Krzywon, Aleksandra; Cortez, Alexander Jorge; Wojtas, Bartosz; Gielniewski, Bartłomiej; Jaksik, Roman; Kimmel, Marek; Widlak, Wieslawa
    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.
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    Transcriptional responses to direct and indirect TGFB1 stimulation in cancerous and noncancerous mammary epithelial cells
    (Springer Nature, 2024) Janus, Patryk; Kuś, Paweł; Jaksik, Roman; Vydra, Natalia; Toma-Jonik, Agnieszka; Gramatyka, Michalina; Kurpas, Monika; Kimmel, Marek; Widłak, Wiesława
    Transforming growth factor beta (TGFβ) is important for the morphogenesis and secretory function of the mammary gland. It is one of the main activators of the epithelial–mesenchymal transition (EMT), a process important for tissue remodeling and regeneration. It also provides cells with the plasticity to form metastases during tumor progression. Noncancerous and cancer cells respond differently to TGFβ. However, knowledge of the cellular signaling cascades triggered by TGFβ in various cell types is still limited.