HSF1, a versatile factor in tumorogenesis.
HSF1 is an essential factor in the acute response to proteotoxic stress, in which it causes rapid transcription of heat shock protein (HSP) genes in order to permit survival of cells and restoration of global protein quality. In addition to this property however, HSF1 is chronically activated or overexpressed in a wide range of cancers and is essential for multiple pathways of malignant transformation. Studies in recent years indicate a remarkable pleiotropy in the properties of HSF1 in cancer. HSF1 functions as a transcription factor for HSP genes, reminiscent of its role in the stress response, and the resultant elevation in HSP levels leads to a reduction in programmed cell death and senescence and permits overexpression of mutated oncogenic protein clients required to fuel tumor growth. In addition HSF1 plays a role as a signal modulator, stimulating kinase activity, regulating energy metabolism and permitting the development of polyploidy in cancer cells. HSF1 can also function as an inhibitor of transcription and in cooperation with NuRD family factors can repress genes that oppose metastasis. Inhibitors of HSF1 are undergoing selection and future studies may see the testing of HSF1 as a target in cancer therapy.
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. scalderw@bidmc.harvard.edu
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D000375:Aging; D016923:Cell Death; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex