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HSF2 cooperates with HSF1 to drive a transcriptional program critical for the malignant state

ABSTRACT: Heat shock factor 1 (HSF1) is well known for its role in the heat shock response (HSR), where it drives a transcriptional program comprising heat shock protein (HSP) genes, and in tumorigenesis, where it drives a program comprising HSPs and many non-canonical target genes that support malignancy. Here, we find that HSF2, an HSF1 paralog with no significant role in the HSR, physically and functionally interacts with HSF1 across diverse types of cancer. HSF1 and HSF2 have strikingly similar chromatin occupancy and regulate a common set of genes which include both HSPs and non-canonical transcriptional targets with roles critical in supporting malignancy. Loss of either HSF1 or HSF2 results in a dysregulated response to nutrient stresses in vitro and reduced tumor progression in cancer cell line xenografts. Taken together, these findings establish HSF2 as a critical cofactor of HSF1 in driving a cancer cell transcriptional program to support the anabolic malignant state.

ORGANISM(S): Homo sapiens

PROVIDER: GSE194098 | GEO | 2022/03/15

REPOSITORIES: GEO

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Sivery2016 - A mammalian heat shock response model

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2012-08-06 | E-GEOD-38912 | biostudies-arrayexpress

HSF1 and HSF2 interactions with chromatin during the heat shock response in mouse spermatocytes

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HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers [ChIP-Seq]

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