PT  - JOURNAL ARTICLE
AU  - Silveira, Maruhen AD
AU  - Tav, Christophe
AU  - Bérube-Simard, Félix-Antoine
AU  - Cuppens, Tania
AU  - Leclercq, Mickaël
AU  - Fournier, Éric
AU  - Côté, Maxime C
AU  - Droit, Arnaud
AU  - Bilodeau, Steve
TI  - Modulating HSF1 levels impacts expression of the estrogen receptor α and antiestrogen response
AID  - 10.26508/lsa.202000811
DP  - 2021 May 01
TA  - Life Science Alliance
PG  - e202000811
VI  - 4
IP  - 5
4099  - http://www.life-science-alliance.org/content/4/5/e202000811.short
4100  - http://www.life-science-alliance.org/content/4/5/e202000811.full
SO  - Life Sci. Alliance2021 May 01; 4
AB  - Master transcription factors control the transcriptional program and are essential to maintain cellular functions. Among them, steroid nuclear receptors, such as the estrogen receptor α (ERα), are central to the etiology of hormone-dependent cancers which are accordingly treated with corresponding endocrine therapies. However, resistance invariably arises. Here, we show that high levels of the stress response master regulator, the heat shock factor 1 (HSF1), are associated with antiestrogen resistance in breast cancer cells. Indeed, overexpression of HSF1 leads to ERα degradation, decreased expression of ERα-activated genes, and antiestrogen resistance. Furthermore, we demonstrate that reducing HSF1 levels reinstates expression of the ERα and restores response to antiestrogens. Last, our results establish a proof of concept that inhibition of HSF1, in combination with antiestrogens, is a valid strategy to tackle resistant breast cancers. Taken together, we are proposing a mechanism where high HSF1 levels interfere with the ERα-dependent transcriptional program leading to endocrine resistance in breast cancer.