Heat Shock Factor 1 (HSF1) as a new tethering factor for ESR1 supporting its action in breast cancer.

Vydra, N.; Janus, P.; Kus, P.; Stokowy, T.; Mrowiec, K.; Toma-Jonik, A.; Krzywon, A.; Cortez, A. J.; Wojtas, B.; Gielniewski, B.; Jaksik, R.; Kimmel, M.; Widlak, W.

doi:10.1101/2021.05.06.442900

bioRxiv · 10.1101/2021.05.06.442900

Heat Shock Factor 1 (HSF1) as a new tethering factor for ESR1 supporting its action in breast cancer.

Vydra, N.·Janus, P.·Kus, P.·Stokowy, T.·Mrowiec, K.·Toma-Jonik, A.·Krzywon, A.·Cortez, A. J.·Wojtas, B.·Gielniewski, B.·Jaksik, R.·Kimmel, M.·Widlak, W.

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Abstract

Heat shock factor 1 (HSF1), a key regulator of transcriptional responses to proteotoxic stress, was recently linked to estrogen (E2) signaling through ESR1. We found that an HSF1 deficiency could lead to the inhibition of the mitogenic action of E2 in breast cancer cells. The stimulatory effect of E2 on the transcriptome is 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 ESR1 to chromatin. HSF1 and ESR1 can cooperate directly in E2-stimulated regulation of transcription, and HSF1 potentiates the action of ESR1 through a mechanism involving chromatin reorganization. Analyses of data from the TCGA database indicate that HSF1 increases the transcriptome diversity in ER-positive breast cancer and can enhance the genomic action of ESR1. Moreover, ESR1 and HSF1 are only prognostic when analyzed together (the worst prognosis for ER-/HSF1high cancers).

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Vydra, N., Janus, P., Kus, P., Stokowy, T., Mrowiec, K., Toma-Jonik, A., Krzywon, A., Cortez, A. J., Wojtas, B., Gielniewski, B., Jaksik, R., Kimmel, M., Widlak, W.. 2021-05-07. Heat Shock Factor 1 (HSF1) as a new tethering factor for ESR1 supporting its action in breast cancer.. https://doi.org/10.1101/2021.05.06.442900

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