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

被引：25

作者：

Smith, Roger S. ^{[1
,2
,3
,4
]}

Takagishi, Seesha R. ^{[1
,2
,3
,5
,6
,19
]}

Amici, David R. ^{[1
,2
,3
,4
]}

Metz, Kyle ^{[1
,2
,3
]}

Gayatri, Sitaram ^{[1
,2
,3
]}

Alasady, Milad J. ^{[1
,2
,3
]}

Wu, Yaqi ^{[1
,2
,3
,7
]}

Brockway, Sonia ^{[1
,2
,3
]}

Taiberg, Stephanie L. ^{[1
,2
,3
]}

Khalatyan, Natalia ^{[2
,8
]}

Taipale, Mikko ^{[9
,10
,11
]}

Santagata, Sandro ^{[12
,13
,14
,15
]}

Whitesell, Luke ^{[10
]}

Lindquist, Susan ^{[16
,17
,18
]}

Savas, Jeffrey N. ^{[2
,8
]}

Mendillo, Marc L. ^{[1
,2
,3
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Biochem & Mol Genet, Chicago, IL 60611 USA

[2] Northwestern Univ, Feinberg Sch Med, Simpson Querrey Inst Epigenet, Chicago, IL 60611 USA

[3] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[4] Northwestern Univ, Feinberg Sch Med, Med Scientist Training Program, Chicago, IL 60611 USA

[5] UCSF, Dept Biochem & Biophys, San Francisco, CA 94158 USA

[6] UCSF, Tetrad Grad Program, San Francisco, CA 94143 USA

[7] Northwestern Univ, Master Biotechnol Program, Evanston, IL 60208 USA

[8] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA

[9] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada

[10] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[11] Canadian Inst Adv Res CIFAR, Mol Architecture Life Program, Toronto, ON, Canada

[12] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[13] Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA

[14] Harvard Med Sch, Lab Syst Pharmacol, Boston, MA 02115 USA

[15] Ludwig Ctr Harvard, Boston, MA 02115 USA

[16] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[17] MIT, Cambridge, MA 02142 USA

[18] Howard Hughes Med Inst, Cambridge, MA 02139 USA

[19] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 11期

关键词：

HEAT-SHOCK FACTOR-2; GENE-TRANSCRIPTION; BINDING ACTIVITY; FACTOR-I; PROTEIN; STRESS; DISTINCT; REVEALS; ACTIVATION; EXPRESSION;

D O I：

10.1126/sciadv.abj6526

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15