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

Roger S. Smith; Seesha R. Takagishi; David R. Amici; Kyle Metz; Sitaram Gayatri; Milad J. Alasady; Yaqi Wu; Sonia Brockway; Stephanie L. Taiberg; Natalia Khalatyan; Mikko Taipale; Sandro Santagata; Luke Whitesell; Susan Lindquist; Jeffrey N. Savas; Marc L. Mendillo

doi:10.1126/sciadv.abj6526

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

Roger S. Smith, Seesha R. Takagishi, David R. Amici, Kyle Metz, Sitaram Gayatri, Milad J. Alasady, Yaqi Wu, Sonia Brockway, Stephanie L. Taiberg, Natalia Khalatyan, Mikko Taipale, Sandro Santagata, Luke Whitesell, Susan Lindquist, Jeffrey N. Savas, Marc L. Mendillo^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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 noncanonical target genes that support malignancy. Here, we find that HSF2, an HSF1 paralog with no substantial role in the HSR, physically and functionally interacts with HSF1 across diverse types of cancer. HSF1 and HSF2 have notably similar chromatin occupancy and regulate a common set of genes that include both HSPs and noncanonical 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. Together, these findings establish HSF2 as a critical cofactor of HSF1 in driving a cancer cell transcriptional program to support the anabolic malignant state.

Original language	English (US)
Article number	abj6526
Journal	Science Advances
Volume	8
Issue number	11
DOIs	https://doi.org/10.1126/sciadv.abj6526
State	Published - Mar 2022

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/sciadv.abj6526

Cite this

Smith, R. S., Takagishi, S. R., Amici, D. R., Metz, K., Gayatri, S., Alasady, M. J., Wu, Y., Brockway, S., Taiberg, S. L., Khalatyan, N., Taipale, M., Santagata, S., Whitesell, L., Lindquist, S., Savas, J. N., & Mendillo, M. L. (2022). HSF2 cooperates with HSF1 to drive a transcriptional program critical for the malignant state. Science Advances, 8(11), Article abj6526. https://doi.org/10.1126/sciadv.abj6526

@article{627faaadb350481e9ab8ac8f6ad56fe0,

title = "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 noncanonical target genes that support malignancy. Here, we find that HSF2, an HSF1 paralog with no substantial role in the HSR, physically and functionally interacts with HSF1 across diverse types of cancer. HSF1 and HSF2 have notably similar chromatin occupancy and regulate a common set of genes that include both HSPs and noncanonical 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. Together, these findings establish HSF2 as a critical cofactor of HSF1 in driving a cancer cell transcriptional program to support the anabolic malignant state.",

author = "Smith, {Roger S.} and Takagishi, {Seesha R.} and Amici, {David R.} and Kyle Metz and Sitaram Gayatri and Alasady, {Milad J.} and Yaqi Wu and Sonia Brockway and Taiberg, {Stephanie L.} and Natalia Khalatyan and Mikko Taipale and Sandro Santagata and Luke Whitesell and Susan Lindquist and Savas, {Jeffrey N.} and Mendillo, {Marc L.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

month = mar,

doi = "10.1126/sciadv.abj6526",

language = "English (US)",

volume = "8",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "11",

}

Smith, RS, Takagishi, SR, Amici, DR, Metz, K, Gayatri, S, Alasady, MJ, Wu, Y, Brockway, S, Taiberg, SL, Khalatyan, N, Taipale, M, Santagata, S, Whitesell, L, Lindquist, S, Savas, JN & Mendillo, ML 2022, 'HSF2 cooperates with HSF1 to drive a transcriptional program critical for the malignant state', Science Advances, vol. 8, no. 11, abj6526. https://doi.org/10.1126/sciadv.abj6526

TY - JOUR

T1 - HSF2 cooperates with HSF1 to drive a transcriptional program critical for the malignant state

AU - Smith, Roger S.

AU - Takagishi, Seesha R.

AU - Amici, David R.

AU - Metz, Kyle

AU - Gayatri, Sitaram

AU - Alasady, Milad J.

AU - Wu, Yaqi

AU - Brockway, Sonia

AU - Taiberg, Stephanie L.

AU - Khalatyan, Natalia

AU - Taipale, Mikko

AU - Santagata, Sandro

AU - Whitesell, Luke

AU - Lindquist, Susan

AU - Savas, Jeffrey N.

AU - Mendillo, Marc L.

PY - 2022/3

Y1 - 2022/3

N2 - 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 noncanonical target genes that support malignancy. Here, we find that HSF2, an HSF1 paralog with no substantial role in the HSR, physically and functionally interacts with HSF1 across diverse types of cancer. HSF1 and HSF2 have notably similar chromatin occupancy and regulate a common set of genes that include both HSPs and noncanonical 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. Together, these findings establish HSF2 as a critical cofactor of HSF1 in driving a cancer cell transcriptional program to support the anabolic malignant state.

AB - 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 noncanonical target genes that support malignancy. Here, we find that HSF2, an HSF1 paralog with no substantial role in the HSR, physically and functionally interacts with HSF1 across diverse types of cancer. HSF1 and HSF2 have notably similar chromatin occupancy and regulate a common set of genes that include both HSPs and noncanonical 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. Together, these findings establish HSF2 as a critical cofactor of HSF1 in driving a cancer cell transcriptional program to support the anabolic malignant state.

UR - http://www.scopus.com/inward/record.url?scp=85126680446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85126680446&partnerID=8YFLogxK

U2 - 10.1126/sciadv.abj6526

DO - 10.1126/sciadv.abj6526

M3 - Article

C2 - 35294249

AN - SCOPUS:85126680446

SN - 2375-2548

VL - 8

JO - Science Advances

JF - Science Advances

IS - 11

M1 - abj6526

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this