HSF2 drives breast cancer progression by acting as a stage-specific switch between proliferation and invasion.

Breast cancer is hallmarked by phenotypic transitions enabling abnormal cell proliferation and invasion. The stress-protective transcription factor heat shock factor 2 (HSF2) is associated with cancer, but its function in breast carcinogenesis remains poorly understood. Analysis of human breast tumor samples and mouse in vivo xenografts uncovered that HSF2 expression and activity undergo dynamic changes as a function of tumor progression.

A guide to heat shock factors as multifunctional transcriptional regulators.

The heat shock factors (HSFs) form a family of transcription factors, which are evolutionarily conserved in eukaryotes. They are best known as transcriptional regulators of molecular chaperone genes, including those encoding heat shock proteins, in response to heat shock and other protein-damaging stresses. Since the discovery of the first HSF and its eponymous role in the heat shock response four decades ago, the currently known HSFs in vertebrates, that is, HSF1-5, HSFX, and HSFY, have been implicated in a wide array of physiological and pathological processes, including organismal development and cancer progression.

Nuclear talin-1 provides a bridge between cell adhesion and gene expression.

Talin-1 (TLN1) is best known to activate integrin receptors and transmit mechanical stimuli to the actin cytoskeleton at focal adhesions. However, the localization of TLN1 is not restricted to focal adhesions. By utilizing both subcellular fractionations and confocal microscopy analyses, we show that TLN1 localizes to the nucleus in several human cell lines, where it is tightly associated with the chromatin.

Proteomic profiling identifies a direct interaction between heat shock transcription factor 2 and the focal adhesion adapter talin-1.

Heat shock factor 2 (HSF2) is a versatile transcription factor that regulates gene expression under stress conditions, during development, and in disease. Despite recent advances in characterizing HSF2-dependent target genes, little is known about the protein networks associated with this transcription factor. In this study, we performed co-immunoprecipitation coupled with mass spectrometry analysis to identify the HSF2 interactome in mouse testes, where HSF2 is required for normal sperm development.

HSFs drive transcription of distinct genes and enhancers during oxidative stress and heat shock.

Reprogramming of transcription is critical for the survival under cellular stress. Heat shock has provided an excellent model to investigate nascent transcription in stressed cells, but the molecular mechanisms orchestrating RNA synthesis during other types of stress are unknown. We utilized PRO-seq and ChIP-seq to study how Heat Shock Factors, HSF1 and HSF2, coordinate transcription at genes and enhancers upon oxidative stress and heat shock.

Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion.

Maintenance of protein homeostasis, through inducible expression of molecular chaperones, is essential for cell survival under protein-damaging conditions. The expression and DNA-binding activity of heat shock factor 2 (HSF2), a member of the heat shock transcription factor family, increase upon exposure to prolonged proteotoxicity. Nevertheless, the specific roles of HSF2 and the global HSF2-dependent gene expression profile during sustained stress have remained unknown.