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

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 non-transformed 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, even these genes 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE38901 | GEO | 2012/08/07

SECONDARY ACCESSION(S): PRJNA169333

REPOSITORIES: GEO

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

Project description: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 non-transformed 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, even these genes 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. ChIP-seq was used to characterize HSF1 binding

2012-08-07 | E-GEOD-38901 | biostudies-arrayexpress

HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers [gene expression]

2012-08-07 | GSE38232 | GEO

HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers [gene expression]

2012-08-06 | E-GEOD-38232 | biostudies-arrayexpress

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

Project description: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.

2022-03-15 | GSE194098 | GEO

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

Project description:This SuperSeries is composed of the following subset Series: GSE38232: HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers [gene expression] GSE38901: HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers [ChIP-Seq] Refer to individual Series

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

The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy

Project description:Stromal cells within the tumor microenvironment are essential for tumor progression and metastasis. Yet surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator Heat-Shock Factor 1 (HSF1) is activated in cancer-associated fibroblasts (CAFs) and is a potent enabler of malignancy. In CAFs, HSF1 drives a transcriptional program that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support the malignant potential of cancer cells in a non-cell-autonomous way and involves two central stromal signaling molecules—TGFβ and stromal-derived factor 1 (SDF1). As clinical confirmation, in early stage breast and lung cancer high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, cancers co-opt the ancient, multifaceted survival functions of HSF1 to orchestrate malignant progression in unexpected ways that have far-reaching therapeutic implications. Gene expression data

2014-07-31 | GSE56252 | GEO

The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy

Project description:Stromal cells within the tumor microenvironment are essential for tumor progression and metastasis. Yet surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator Heat-Shock Factor 1 (HSF1) is activated in cancer-associated fibroblasts (CAFs) and is a potent enabler of malignancy. In CAFs, HSF1 drives a transcriptional program that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support the malignant potential of cancer cells in a non-cell-autonomous way and involves two central stromal signaling moleculesM-bM-^@M-^TTGFM-NM-2 and stromal-derived factor 1 (SDF1). As clinical confirmation, in early stage breast and lung cancer high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, cancers co-opt the ancient, multifaceted survival functions of HSF1 to orchestrate malignant progression in unexpected ways that have far-reaching therapeutic implications. Gene expression data We used microarrays to examine the HSF1-dependent effect of co-culture on gene expression in cancer cells and fibroblasts. D2A1 mouse breast cancer cells were co-cultured with WT or Hsf1 null MEFs for 72h, afterwhich the two cell types were separated from each other by FACS and analyzed. Each cell type was also grown separately, as control.

2014-07-31 | E-GEOD-56252 | biostudies-arrayexpress

Heat Shock Factor 1 drives intergenic association of its target gene loci during heat shock

Project description:Transcriptional induction of Heat Shock Protein (HSP) genes in yeast is accompanied by dynamic changes in their 3D structure and spatial organization, yet the molecular basis for these phenomena remains unknown. Using chromosome conformation capture and single cell imaging, we show that genes transcriptionally activated by Heat Shock Factor 1 (Hsf1) specifically interact across chromosomes and coalesce into diffraction-limited intranuclear foci. Genes activated by the alternative stress regulators Msn2 and Msn4, in contrast, do not interact among themselves nor with Hsf1 targets. Likewise, constitutively expressed genes, even those interposed between HSP genes, show no detectable interaction. Hsf1 forms discrete subnuclear puncta when stressactivated, and these puncta dissolve in concert with transcriptional attenuation, paralleling the kinetics of HSP gene coalescence and dissolution. Nuclear Hsf1 and RNA Pol II are both necessary for intergenic HSP gene interactions, while DNA-bound Hsf1 is necessary and sufficient to drive coalescence of a heterologous gene. Our findings demonstrate that Hsf1 can dynamically restructure the yeast genome.

2018-11-20 | GSE122666 | GEO

Genome-wide characterization of HSF1 binding in human WT and FBXW7 KO colon cancer cells under basal conditions and upon heat shock

Project description:FBXW7 modulates stress response by post-translational modification of HSF1 HSF1 orchestrates the heat-shock response upon exposure to heat stress and activates a transcriptional program vital for cancer cells. In this study we assayed for genome-wide localization of HSF1 enrichment in the HCT116 FBXW7 KO colon cells and their wild type counterpart in untreated cells and upon heat shock. These results revealed that accumulation of nuclear HSF1 in FBXW7 KO cells results in rewiring of the HSF1 transcriptional program.

2015-02-20 | GSE57398 | GEO

Identification of HSF1- target genes involved in thermal stress in the Pacific oyster Crassostrea gigas by ChIP-seq

Project description:The Pacific oyster Crassostrea gigas, a commercially important species inhabiting the intertidal zone, can tolerate temperature fluctuations. Heat shock transcription factor 1 (HSF1) plays an important role in the process of resistance of thermal stress. However, HSF1 has not been fully characterized in the Pacific oyster. C. gigas with an expansion of heat shock protein (HSP) 70. In this study, we analyzed genes regulated by HSF1 in response to heat shock by Chromatin immunoprecipitation followed sequencing (ChIP-seq), determined the expression patterns of target genes by qRT-PCR, and validated the regulatory relationship between one HSP70 and HSF1. We found 916 peaks corresponding to specific binding sites of HSF1, and peaks were annotated to nearest genes. In Gene Ontology analysis, HSF1 target genes was related to signal transduction, energy production, and response to biotic stimulus. Four HSP70 genes, two HSP40 genes, and one small HSP gene exhibited binding to HSF1. One HSP70 with a binding site in the promoter region was validated to be regulated by HSF1 under heat shock. These results provide a basis for future studies aimed at determining the mechanisms underlying thermal tolerance and provide insights into gene regulation in the Pacific oyster.

2020-10-16 | GSE138959 | GEO

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