title: Proteotoxicity is not the reason for the dependence of cancer cells on the major chaperone Hsp70.
abstract: Several years ago a hypothesis was proposed that the survival of cancer cells depend on elevated expression of molecular chaperones because these cells are prone to proteotoxic stress. A critical prediction of this hypothesis is that depletion of chaperones in cancer cells should lead to proteotoxicity. Here, using the major chaperone Hsp70 as example, we demonstrate that its depletion does not trigger proteotoxic stress, thus refuting the model. Accordingly, other functions of chaperones, e.g., their role in cell signaling, might define the requirements for chaperones in cancer cells, which is critical for rational targeting Hsp70 in cancer treatment.
authors.affiliation: Department of Biochemistry; Boston University School of Medicine; Boston, MA USA; Department of Medicine; Boston University School of Medicine; Boston, MA USA.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Colvin
authors.affiliation: Department of Biochemistry; Boston University School of Medicine; Boston, MA USA.
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Gabai
authors.affiliation: Department of Biochemistry; Boston University School of Medicine; Boston, MA USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Sherman
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D061986:MCF-7 Cells; D058849:Protein Refolding; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018840:HSP70 Heat-Shock Proteins
keywords: Hsp70; chaperone; non-oncogene addiction; proteotoxic stress; rational drug targeting