RT Journal Article
SR Electronic
T1 Modulating HSF1 levels impacts expression of the estrogen receptor α and antiestrogen response
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000811
DO 10.26508/lsa.202000811
VO 4
IS 5
A1 Maruhen AD Silveira
A1 Christophe Tav
A1 Félix-Antoine Bérube-Simard
A1 Tania Cuppens
A1 Mickaël Leclercq
A1 Éric Fournier
A1 Maxime C Côté
A1 Arnaud Droit
A1 Steve Bilodeau
YR 2021
UL https://www.life-science-alliance.org/content/4/5/e202000811.abstract
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.