title: Unusual Suspects in the Twilight Zone Between the Hsp90 Interactome and Carcinogenesis.
abstract: The molecular chaperone Hsp90 has attracted a lot of interest in cancer research ever since cancer cells were found to be more sensitive to Hsp90 inhibition than normal cells. Why that is has remained a matter of debate and is still unclear. In addition to increased Hsp90 dependence for some mutant cancer proteins and modifications of the Hsp90 machinery itself, a number of other characteristics of cancer cells probably contribute to this phenomenon; these include aneuploidy and overall increased numbers and levels of defective and mutant proteins, which all contribute to perturbed proteostasis. Work over the last two decades has demonstrated that many cancer-related proteins are Hsp90 clients, and yet only few of them have been extensively investigated, selected either on the basis of their obvious function as cancer drivers or because they proved to be convenient biomarkers for monitoring the effects of Hsp90 inhibitors. The purpose of our review is to go beyond these "usual suspects." We established a workflow to select poorly studied proteins that are related to cancer processes and qualify as Hsp90 clients. By discussing and taking a fresh look at these "unusual suspects," we hope to stimulate others to revisit them as novel therapeutic targets or diagnostic markers.
authors.affiliation: Département de Biologie Cellulaire, Université de Genève, Sciences III, Geneva, Switzerland.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Vartholomaiou
authors.affiliation: Département de Biologie Cellulaire, Université de Genève, Sciences III, Geneva, Switzerland.
authors.forename: Pablo C
authors.initials: PC
authors.lastname: Echeverría
authors.affiliation: Département de Biologie Cellulaire, Université de Genève, Sciences III, Geneva, Switzerland. Electronic address: didier.picard@unige.ch.
authors.forename: Didier
authors.initials: D
authors.lastname: Picard
mesh_terms: D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D028884:Karyopherins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D015513:Oncogene Proteins / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000097606:Exportin 1 Protein; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; D054316:Biomarkers, Pharmacological; D018797:Cell Cycle Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D018841:HSP90 Heat-Shock Proteins; D011495:Histone-Lysine N-Methyltransferase; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D011484:Protein-Arginine N-Methyltransferases; D053484:RecQ Helicases; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097606:Exportin 1 Protein; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C410024:BRMS1 protein, human; C400529:PRMT5 protein, human; C506278:SMYD3 protein, human; C097151:Bloom syndrome protein
keywords: Hsp90; Kinase; Molecular chaperone; Oncogene; Protein–protein interaction; Regulation; Transcription factor; Tumor suppressor