title: Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update.
abstract: Heat shock proteins (HSP) are a subset of the molecular chaperones, best known for their rapid and abundant induction by stress. HSP genes are activated at the transcriptional level by heat shock transcription factor 1 (HSF1). During the progression of many types of cancer, this heat shock transcriptional regulon becomes co-opted by mechanisms that are currently unclear, although evidently triggered in the emerging tumor cell. Concerted activation of HSF1 and the accumulation of HSPs then participate in many of the traits that permit the malignant phenotype. Thus, cancers of many histologies exhibit activated HSF1 and increased HSP levels that may help to deter tumor suppression and evade therapy in the clinic. We review here the extensive work that has been carried out and is still in progress aimed at (1) understanding the oncogenic mechanisms by which HSP genes are switched on, (2) determining the roles of HSF1/HSP in malignant transformation and (3) discovering approaches to therapy based on disrupting the influence of the HSF1-controlled transcriptome in cancer.
authors.affiliation: Oncology Laboratory, Institute of Experimental Medicine and Biology of Cuyo (IMBECU), Scientific and Technological Center (CCT), CONICET, 5500 Mendoza, Argentina. dciocca@mendoza-conicet.gob.ar.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Ciocca
authors.affiliation: Apoptosis Cancer and Development, Cancer Research Center of Lyon (CRCL), UMR INSERM 1052-CNRS 5286, Claude Bernard University, Lyon-1, Cheney A Building, Centre Regional Léon Bérard, 28, rue Laennec 69008 LYON, France. parrigo@me.com; arrigo@univ-lyon1.fr.
authors.forename: Andre Patrick
authors.initials: AP
authors.lastname: Arrigo
authors.affiliation: Molecular and Cellular Radiation Oncology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA02215.
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Calderwood
mesh_terms: D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018834:Chaperonin 60; D004268:DNA-Binding Proteins; C476884:HOPX protein, human; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins; D018832:Molecular Chaperones; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins