HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers

Marc L. Mendillo, Sandro Santagata, Martina Koeva, George W. Bell, Rong Hu, Rulla M. Tamimi, Ernest Fraenkel, Tan Ince, Luke Whitesell, Susan Lindquist

Research output: Contribution to journalArticle

312 Citations (Scopus)

Abstract

Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival, and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their nontransformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, many are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.

Original languageEnglish
Pages (from-to)549-562
Number of pages14
JournalCell
Volume150
Issue number3
DOIs
StatePublished - Aug 3 2012

Fingerprint

Shock
Hot Temperature
Heat-Shock Response
Neoplasms
Heat-Shock Proteins
Genes
Gene Regulatory Networks
Neoplasm Genes
Cells
Transcriptome
Cell Survival
Cell Cycle
Colon
Carcinogenesis
Breast
Cell Proliferation
Metabolism
Neoplasm Metastasis
Tumors
Lung

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mendillo, M. L., Santagata, S., Koeva, M., Bell, G. W., Hu, R., Tamimi, R. M., ... Lindquist, S. (2012). HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell, 150(3), 549-562. https://doi.org/10.1016/j.cell.2012.06.031

HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. / Mendillo, Marc L.; Santagata, Sandro; Koeva, Martina; Bell, George W.; Hu, Rong; Tamimi, Rulla M.; Fraenkel, Ernest; Ince, Tan; Whitesell, Luke; Lindquist, Susan.

In: Cell, Vol. 150, No. 3, 03.08.2012, p. 549-562.

Research output: Contribution to journalArticle

Mendillo, ML, Santagata, S, Koeva, M, Bell, GW, Hu, R, Tamimi, RM, Fraenkel, E, Ince, T, Whitesell, L & Lindquist, S 2012, 'HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers', Cell, vol. 150, no. 3, pp. 549-562. https://doi.org/10.1016/j.cell.2012.06.031
Mendillo, Marc L. ; Santagata, Sandro ; Koeva, Martina ; Bell, George W. ; Hu, Rong ; Tamimi, Rulla M. ; Fraenkel, Ernest ; Ince, Tan ; Whitesell, Luke ; Lindquist, Susan. / HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. In: Cell. 2012 ; Vol. 150, No. 3. pp. 549-562.
@article{cd007d375e0e4e93bc6a8fb1e9f1ac84,
title = "HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers",
abstract = "Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival, and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their nontransformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, many are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.",
author = "Mendillo, {Marc L.} and Sandro Santagata and Martina Koeva and Bell, {George W.} and Rong Hu and Tamimi, {Rulla M.} and Ernest Fraenkel and Tan Ince and Luke Whitesell and Susan Lindquist",
year = "2012",
month = "8",
day = "3",
doi = "10.1016/j.cell.2012.06.031",
language = "English",
volume = "150",
pages = "549--562",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers

AU - Mendillo, Marc L.

AU - Santagata, Sandro

AU - Koeva, Martina

AU - Bell, George W.

AU - Hu, Rong

AU - Tamimi, Rulla M.

AU - Fraenkel, Ernest

AU - Ince, Tan

AU - Whitesell, Luke

AU - Lindquist, Susan

PY - 2012/8/3

Y1 - 2012/8/3

N2 - Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival, and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their nontransformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, many are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.

AB - Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival, and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their nontransformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, many are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.

UR - http://www.scopus.com/inward/record.url?scp=84864585171&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864585171&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2012.06.031

DO - 10.1016/j.cell.2012.06.031

M3 - Article

C2 - 22863008

AN - SCOPUS:84864585171

VL - 150

SP - 549

EP - 562

JO - Cell

JF - Cell

SN - 0092-8674

IS - 3

ER -