Skip to main content
SpringerLink
Log in

HSP90-Based Heterocomplex as Essential Regulator for Cancer Disease

  • Chapter
  • First Online:
Heat Shock Protein 90 in Human Diseases and Disorders

Part of the book series: Heat Shock Proteins ((HESP,volume 19))

  • 513 Accesses

Abstract

Heat-shock protein 90 (HSP90) is a molecular chaperone that represents the most abundant soluble protein of the cell. This chaperone shows intrinsic ATPase activity and associates to a great number of client factors such as steroid receptors, tyrosine-kinases, transcription factors, enzymes, cytoskeletal proteins, channels, histones, etc. Because of these interactions, HSP90 is implicated in diverse biological processes that require critical and coordinated regulatory mechanisms to modulate its activity. HSP90 forms heterocomplexes with other chaperones and co-chaperones such as TPR-domain immunophilins that modulate HSP90 properties and are themselves subject of regulation. In malignancy, HSP90 is essential to preserve the metastable forms of oncoproteins that are usually mutated, overamplified, and sometimes translocated from their normal subcellular compartments. Thus, HSP90 helps to buffer the proteostasis of the cell that is assaulted by the onset of the stress generated by the malignant condition. Consequently, HSP90 is an attractive pharmacologic target, and the pharmaceutical industry has generated over the last years several advances in both the basic biology and the translational drug development around HSP90. This chapter is focused on the multiple aspects by which the HSP90 activity and that related to HSP90-binding proteins, particularly immunophilins, are regulated in malignancy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CyP:

Cyclophilin

FKBP:

FK506-Binding Protein

GA:

Geldanamycin

HSP:

Heat-shock protein

hTERT:

Reverse transcriptase subunit of human telomerase

TPR:

Tetratricopeptide repeats

References

  • Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, Prodromou C, Pearl LH (2006) Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 440:1013–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ansa-Addo EA, Thaxton J, Hong F et al (2016) Clients and oncogenic roles of molecular chaperone gp96/grp94. Curr Top Med Chem 16:2765–2778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ashida T, Kikuchi T (2013) Estimation of relative binding free energy based on a free energy variational principle for the FKBP-ligand system. J Comput Aided Mol Des 27:479–490

    Article  CAS  PubMed  Google Scholar 

  • Aziz F (2016) The emerging role of miR-223 as novel potential diagnostic and therapeutic target for inflammatory disorders. Cell Immunol 303:1–6

    Article  CAS  PubMed  Google Scholar 

  • Bakthisaran R, Tangirala R, Rao Ch M (2015) Small heat shock proteins: role in cellular functions and pathology. Biochim Biophys Acta 1854:291–319

    Article  CAS  PubMed  Google Scholar 

  • Barik S (2006) Immunophilins: for the love of proteins. Cell Mol Life Sci 63:2889–2900

    Article  CAS  PubMed  Google Scholar 

  • Becker B, Multhoff G, Farkas B, Wild PJ, Landthaler M, Stolz W, Vogt T (2004) Induction of Hsp90 protein expression in malignant melanomas and melanoma metastases. Exp Dermatol 13:27–32

    Article  CAS  PubMed  Google Scholar 

  • Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Pütz B, Papiol S, Seaman S, Lucae S, Kohli MA, Nickel T, Künzel HE, Fuchs B, Majer M, Pfennig A, Kern N, Brunner J, Modell S, Baghai T, Deiml T, Zill P, Bondy B, Rupprecht R, Messer T, Köhnlein O, Dabitz H, Brückl T, Müller N, Pfister H, Lieb R, Mueller JC, Lõhmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B (2004) Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 36:1319–1325

    Article  CAS  PubMed  Google Scholar 

  • Bohne AV, Schwenkert S, Grimm B, Nickelsen J (2016) Roles of tetratricopeptide repeat proteins in biogenesis of the photosynthetic apparatus. Int Rev Cell Mol Biol 324:187–227

    Article  CAS  PubMed  Google Scholar 

  • Bonner JM, Boulianne GL (2017) Diverse structures, functions and uses of FK506 binding proteins. Cell Signal 38:97–105

    Article  CAS  PubMed  Google Scholar 

  • Bracken CP, Scott HS, Goodall GJ (2016) A network-biology perspective of microRNA function and dysfunction in cancer. Nat Rev Genet 17:719–732

    Article  CAS  PubMed  Google Scholar 

  • Brady CA, Attardi LD (2010) p53 at a glance. J Cell Sci 123:2527–2532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brough PA, Aherne W, Barril X et al (2008) 4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer. J Med Chem 51:196–218

    Article  CAS  PubMed  Google Scholar 

  • Calado RT, Young NS (2009) Telomere diseases. N Engl J Med 361:2353–2365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calderwood SK (2018) Heat shock proteins and cancer: intracellular chaperones or extracellular signalling ligands? Philos Trans R Soc Lond B Biol Sci 373(1738). pii: 20160524. https://doi.org/10.1098/rstb.2016.0524

  • Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumourigenesis. Trends Biochem Sci 31:164–172

    Article  CAS  PubMed  Google Scholar 

  • Chatterjee S, Burns TF (2017) Targeting heat shock proteins in cancer: a promising therapeutic approach. Int J Mol Sci 18, 18(9). pii: E1978. https://doi.org/10.3390/ijms18091978

  • Chen WY, Chang FR, Huang ZY, Chen JH, Wu YC, Wu CC (2008) Tubocapsenolide-A, a novel withanolide, inhibits proliferation and induces apoptosis in MDA-MB-231 cells by thiol oxidation of heat shock proteins. J Biol Chem 283:17184–17193

    Article  CAS  PubMed  Google Scholar 

  • Chiosis G, Timaul MN, Lucas B, Munster PN, Zheng FF, Sepp-Lorenzino L, Rosen N (2001) A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells. Chem Biol 8:289–299

    Article  CAS  PubMed  Google Scholar 

  • Clarke PA, Hostein I, Banerji U, Stefano FD, Maloney A, Walton M, Judson I, Workman P (2000) Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of the hsp90 molecular chaperone. Oncogene 19:4125–4133

    Article  CAS  PubMed  Google Scholar 

  • Clevenger RC, Blagg BS (2004) Design, synthesis, and evaluation of a radicicol and geldanamycin chimera, radamide. Org Lett 6:4459–4462

    Article  CAS  PubMed  Google Scholar 

  • Clevers H (2011) The cancer stem cell: premises, promises and challenges. Nat Med 17:313–319

    Article  CAS  PubMed  Google Scholar 

  • Colo GP, Rubio MF, Nojek IM, Werbajh SE, Echeverria PC, Alvarado CV, Nahmod VE, Galigniana MD, Costas MA (2008) The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action. Oncogene 27:2430–2444

    Article  CAS  PubMed  Google Scholar 

  • Cowen LE, Lindquist S (2005) Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science 309:2185–2189

    Article  CAS  PubMed  Google Scholar 

  • da Silva VC, Ramos CH (2012) The network interaction of the human cytosolic 90 kDa heat shock protein Hsp90: a target for cancer therapeutics. J Proteome 75:2790–2802

    Article  CAS  Google Scholar 

  • Dimas DT, Perlepe CD, Sergentanis TN, Misitzis I, Kontzoglou K, Patsouris E, Kouraklis G, Psaltopoulou T, Nonni A (2018) The prognostic significance of Hsp70/Hsp90 expression in breast cancer: a systematic review and meta-analysis. Anticancer Res 38:1551–1562

    CAS  PubMed  Google Scholar 

  • Dumont FJ (2000) FK506, an immunosuppressant targeting calcineurin function. Curr Med Chem 7:731–748

    Article  CAS  PubMed  Google Scholar 

  • Ebong IO, Beilsten-Edmands V, Patel NA, Morgner N, Robinson CV (2016) The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes. Cell Discov 2:16002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Echeverria PC, Picard D (2010) Molecular chaperones, essential partners of steroid hormone receptors for activity and mobility. Biochim Biophys Acta 1803:641–649

    Article  CAS  PubMed  Google Scholar 

  • Ehrenfried JA, Herron BE, Townsend CM Jr, Evers BM (1995) Heat shock proteins are differentially expressed in human gastrointestinal cancers. Surg Oncol 4:197–203

    Article  CAS  PubMed  Google Scholar 

  • Eisenstein M (2011) Telomeres: all’s well that ends well. Nature 478:S13–S15

    Article  CAS  PubMed  Google Scholar 

  • Ellis RJ (1993) The general concept of molecular chaperones. Philos Trans R Soc Lond Ser B Biol Sci 339:257–261

    Article  CAS  Google Scholar 

  • Ellis RJ (1996) Discovery of molecular chaperones. Cell Stress Chaperones 111:155–160

    Article  Google Scholar 

  • Erlejman AG, Lagadari M, Galigniana MD (2013) Hsp90-binding immunophilins as a potential new platform for drug treatment. Future Med Chem 5:591–607

    Article  CAS  PubMed  Google Scholar 

  • Erlejman AG, De Leo SA, Mazaira GI, Molinari AM, Camisay MF, Fontana V, Cox MB, Piwien-Pilipuk G, Galigniana MD (2014a) NF-kappaB transcriptional activity is modulated by FK506-binding proteins FKBP51 and FKBP52: a role for peptidyl-prolyl isomerase activity. J Biol Chem 289:26263–26276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erlejman AG, Lagadari M, Toneatto J, Piwien-Pilipuk G, Galigniana MD (2014b) Regulatory role of the 90-kDa-heat-shock protein (Hsp90) and associated factors on gene expression. Biochim Biophys Acta 1839:71–87

    Article  CAS  PubMed  Google Scholar 

  • Eustace BK, Jay DG (2004) Extracellular roles for the molecular chaperone, hsp90. Cell Cycle 3:1098–1100

    Article  CAS  PubMed  Google Scholar 

  • Eustace BK, Sakurai T, Stewart JK et al (2004) Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Nat Cell Biol 6:507–514

    Article  CAS  PubMed  Google Scholar 

  • Fan AC, Young JC (2011) Function of cytosolic chaperones in Tom70-mediated mitochondrial import. Protein Pept Lett 18:122–131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng X, Pomplun S, Hausch F (2015) Recent progress in FKBP ligand development. Curr Mol Pharmacol 9:27–36

    Article  CAS  PubMed  Google Scholar 

  • Ferrarini M, Heltai S, Zocchi MR, Rugarli C (1992) Unusual expression and localization of heat-shock proteins in human tumour cells. Int J Cancer 51:613–619

    Article  CAS  PubMed  Google Scholar 

  • Gaali S, Kirschner A, Cuboni S et al (2015) Selective inhibitors of the FK506-binding protein 51 by induced fit. Nat Chem Biol 11:33–37

    Article  CAS  PubMed  Google Scholar 

  • Galigniana MD (2012) Steroid receptor coupling becomes nuclear. Chem Biol 19:662–663

    Article  CAS  PubMed  Google Scholar 

  • Galigniana MD, Radanyi C, Renoir JM, Housley PR, Pratt WB (2001) Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus. J Biol Chem 276:14884–14889

    Article  CAS  PubMed  Google Scholar 

  • Galigniana MD, Harrell JM, O’Hagen HM, Ljungman M, Pratt WB (2004) Hsp90-binding immunophilins link p53 to dynein during p53 transport to the nucleus. J Biol Chem 279:22483–22489

    Article  CAS  PubMed  Google Scholar 

  • Galigniana MD, Echeverria PC, Erlejman AG, Piwien-Pilipuk G (2010a) Role of molecular chaperones and TPR-domain proteins in the cytoplasmic transport of steroid receptors and their passage through the nuclear pore. Nucleus 1:299–308

    Article  PubMed  PubMed Central  Google Scholar 

  • Galigniana MD, Erlejman AG, Monte M, Gomez-Sanchez C, Piwien-Pilipuk G (2010b) The hsp90-FKBP52 complex links the mineralocorticoid receptor to motor proteins and persists bound to the receptor in early nuclear events. Mol Cell Biol 30:1285–1298

    Article  CAS  PubMed  Google Scholar 

  • Galigniana NM, Ballmer LT, Toneatto J, Erlejman AG, Lagadari M, Galigniana MD (2012) Regulation of the glucocorticoid response to stress-related disorders by the Hsp90-binding immunophilin FKBP51. J Neurochem 122:4–18

    Article  CAS  PubMed  Google Scholar 

  • Gallo LI, Ghini AA, Piwien Pilipuk G, Galigniana MD (2007) Differential recruitment of tetratricorpeptide repeat domain immunophilins to the mineralocorticoid receptor influences both heat-shock protein 90-dependent retrotransport and hormone-dependent transcriptional activity. Biochemistry 46:14044–14057

    Article  CAS  PubMed  Google Scholar 

  • Gallo LI, Lagadari M, Piwien-Pilipuk G, Galigniana MD (2011) The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is a mitochondrial protein that translocates to the nucleus to protect cells against oxidative stress. J Biol Chem 286:30152–30160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giordano A, Avellino R, Ferraro P, Romano S, Corcione N, Romano MF (2006) Rapamycin antagonizes NF-kappaB nuclear translocation activated by TNF-alpha in primary vascular smooth muscle cells and enhances apoptosis. Am J Physiol Heart Circ Physiol 290:H2459–H2465

    Article  CAS  PubMed  Google Scholar 

  • Gomes NM, Shay JW, Wright WE (2010) Telomere biology in Metazoa. FEBS Lett 584:3741–3751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gougelet A, Bouclier C, Marsaud V, Maillard S, Mueller SO, Korach KS, Renoir JM (2005) Estrogen receptor alpha and beta subtype expression and transactivation capacity are differentially affected by receptor-, hsp90- and immunophilin-ligands in human breast cancer cells. J Steroid Biochem Mol Biol 94:71–81

    Article  CAS  PubMed  Google Scholar 

  • Grossmann C, Ruhs S, Langenbruch L, Mildenberger S, Stratz N, Schumann K, Gekle M (2012) Nuclear shuttling precedes dimerization in mineralocorticoid receptor signaling. Chem Biol 19:742–751

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  • Hao H, Naomoto Y, Bao X et al (2010) HSP90 and its inhibitors. Oncol Rep 23:1483–1492

    CAS  PubMed  Google Scholar 

  • Haque A, Alam Q, Alam MZ, Azhar EI, Sait KH, Anfinan N, Mushtaq G, Kamal MA, Rasool M (2016) Current understanding of HSP90 as a novel therapeutic target: an emerging approach for the treatment of cancer. Curr Pharm Des 22:2947–2959

    Article  CAS  PubMed  Google Scholar 

  • Harley CB (2008) Telomerase and cancer therapeutics. Nat Rev Cancer 8:167–179

    Article  CAS  PubMed  Google Scholar 

  • Harrell JM, Kurek I, Breiman A, Radanyi C, Renoir JM, Pratt WB, Galigniana MD (2002) All of the protein interactions that link steroid receptor-hsp90.immunophilin heterocomplexes to cytoplasmic dynein are common to plant and animal cells. Biochemistry 41:5581–5587

    Article  CAS  PubMed  Google Scholar 

  • Hoang AT, Huang J, Rudra-Ganguly N, Zheng J, Powell WC, Rabindran SK, Wu C, Roy-Burman P (2000) A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma. Am J Pathol 156:857–864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancers. Science 253:49–53

    Article  CAS  PubMed  Google Scholar 

  • Holt SE, Aisner DL, Baur J et al (1999) Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev 13:817–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoter A, El-Sabban ME, Naim HY (2018) The HSP90 family: structure, regulation, function, and implications in health and disease. Int J Mol Sci 19(9). pii: E2560. doi: https://doi.org/10.3390/ijms19092560

  • Huang SL, Chao CC (2015) Silencing of taxol-sensitizer genes in cancer cells: lack of sensitization effects. Cancer 7:1052–1071

    Article  CAS  Google Scholar 

  • Iwasaki S, Kobayashi M, Yoda M, Sakaguchi Y, Katsuma S, Suzuki T, Tomari Y (2010) Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes. Mol Cell 39:292–299

    Article  CAS  PubMed  Google Scholar 

  • Jeong YY, Her J, Oh SY, Chung IK (2016) Hsp90-binding immunophilin FKBP52 modulates telomerase 1069 activity by promoting the cytoplasmic retrotransport of hTERT. Biochem J 473:3517–3532

    Article  CAS  PubMed  Google Scholar 

  • Jeong JH, Oh YJ, Kwon TK, Seo YH (2017) Chalcone-templated Hsp90 inhibitors and their effects on gefitinib resistance in non-small cell lung cancer (NSCLC). Arch Pharm Res 40:96–105

    Article  CAS  PubMed  Google Scholar 

  • Jhaveri K, Ochiana SO, Dunphy MP et al (2014) Heat shock protein 90 inhibitors in the treatment of cancer: current status and future directions. Expert Opin Investig Drugs 23:611–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang W, Cazacu S, Xiang C, Zenklusen JC, Fine HA, Berens M, Armstrong B, Brodie C, Mikkelsen T (2008) FK506 binding protein mediates glioma cell growth and sensitivity to rapamycin treatment by regulating NF-kappaB signaling pathway. Neoplasia 10:235–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jorge S, Lucena-Araujo AR, Yasuda H et al (2018) EGFR exon 20 insertion mutations display sensitivity to Hsp90 inhibition in preclinical models and lung adenocarcinomas. Clin Cancer Res 24:6548–6555

    Article  PubMed  PubMed Central  Google Scholar 

  • Kach J, Conzen SD, Szmulewitz RZ (2015) Targeting the glucocorticoid receptor in breast and prostate cancers. Sci Transl Med 7:305ps319. https://doi.org/10.1126/scitranslmed.aac7531

    Article  CAS  Google Scholar 

  • Kim HL, Cassone M, Otvos L Jr, Vogiatzi P (2008) HIF-1alpha and STAT3 client proteins interacting with the cancer chaperone Hsp90: therapeutic considerations. Cancer Biol Ther 7:10–14

    Article  CAS  PubMed  Google Scholar 

  • Kovacs JJ, Murphy PJ, Gaillard S et al (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18:601–607

    Article  CAS  PubMed  Google Scholar 

  • Kwon HJ, Yoshida M, Fukui Y, Horinouchi S, Beppu T (1992) Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol. Cancer Res 52:6926–6930

    CAS  PubMed  Google Scholar 

  • Lagadari M, Zgajnar NR, Gallo LI, Galigniana MD (2016) Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity. Mol Oncol 10:1086–1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lampis A, Carotenuto P, Vlachogiannis G et al (2018) MIR21 drives resistance to heat shock protein 90 inhibition in cholangiocarcinoma. Gastroenterology 154:1066–1079 e1065

    Article  CAS  PubMed  Google Scholar 

  • Langer T, Rosmus S, Fasold H (2003) Intracellular localization of the 90 kDA heat shock protein (HSP90alpha) determined by expression of a EGFP-HSP90alpha-fusion protein in unstressed and heat stressed 3T3 cells. Cell Biol Int 27:47–52

    Article  CAS  PubMed  Google Scholar 

  • Lebeau J, Le Chalony C, Prosperi MT, Goubin G (1991) Constitutive overexpression of a 89 kDa heat shock protein gene in the HBL100 human mammary cell line converted to a tumourigenic phenotype by the EJ/T24 Harvey-ras oncogene. Oncogene 6:1125–1132

    CAS  PubMed  Google Scholar 

  • Li J, Buchner J (2013) Structure, function and regulation of the hsp90 machinery. Biom J 36:106–117

    Google Scholar 

  • Li W, Li Y, Guan S, Fan J, Cheng CF, Bright AM, Chinn C, Chen M, Woodley DT (2007) Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing. EMBO J 26:1221–1233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Zhang T, Jiang Y, Lee HF, Schwartz SJ, Sun D (2009) Epigallocatechin-3-gallate inhibits Hsp90 function by impairing Hsp90 association with cochaperones in pancreatic cancer cell line Mia Paca-2. Mol Pharm 6:1152–1159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li W, Tsen F, Sahu D, Bhatia A, Chen M, Multhoff G, Woodley DT (2013) Extracellular Hsp90 (eHsp90) as the actual target in clinical trials: intentionally or unintentionally. Int Rev Cell Mol Biol 303:203–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin JF, Xu J, Tian HY, Gao X, Chen QX, Gu Q, Xu GJ, Song JD, Zhao FK (2007) Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis. Int J Cancer 121:2596–2605

    Article  CAS  PubMed  Google Scholar 

  • Liu F, Wang YQ, Meng L, Gu M, Tan RY (2013a) FK506-binding protein 12 ligands: a patent review. Expert Opin Ther Pat 23:1435–1449

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Xiao F, Serebriiskii IG et al (2013b) Network analysis identifies an HSP90-central hub susceptible in ovarian cancer. Clin Cancer Res 19:5053–5067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S (2005) S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A 102:8525–8530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matthews SB, Vielhauer GA, Manthe CA, Chaguturu VK, Szabla K, Matts RL, Donnelly AC, Blagg BS, Holzbeierlein JM (2010) Characterization of a novel novobiocin analogue as a putative C-terminal inhibitor of heat shock protein 90 in prostate cancer cells. Prostate 70:27–36

    Article  CAS  PubMed  Google Scholar 

  • Mayer MP (2010) Gymnastics of molecular chaperones. Mol Cell 39:321–331

    Article  CAS  PubMed  Google Scholar 

  • Mazaira GI, Lagadari M, Erlejman AG, Galigniana MD (2014) The emerging role of TPR-domain immunophilins in the mechanism of action of steroid receptors. Nucl Recept Res 1:1–17. https://doi.org/10.11131/2014/101094. ID:101094

    Article  Google Scholar 

  • Mazaira GI, Zgajnar NR, Lotufo CM, Daneri-Becerra C, Sivils JC, Soto OB, Cox MB, Galigniana MD (2018) The nuclear receptor field: a historical overview and future challenges. Nucl Recept Res 5:101320. https://doi.org/10.11131/2018/101320

    Article  Google Scholar 

  • Mellatyar H, Talaei S, Pilehvar-Soltanahmadi Y, Barzegar A, Akbarzadeh A, Shahabi A, Barekati-Mowahed M, Zarghami N (2018) Targeted cancer therapy through 17-DMAG as an Hsp90 inhibitor: overview and current state of the art. Biomed Pharmacother = Biomedecine Pharmacotherapie 102:608–617

    Article  CAS  PubMed  Google Scholar 

  • Meyer P, Prodromou C, Liao C et al (2004) Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery. EMBO J 23:1402–1410

    Article  CAS  PubMed  Google Scholar 

  • Miyoshi T, Takeuchi A, Siomi H, Siomi MC (2010) A direct role for Hsp90 in pre-RISC formation in Drosophila. Nat Struct Mol Biol 17:1024–1026

    Article  CAS  PubMed  Google Scholar 

  • Mollapour M, Neckers L (2012) Post-translational modifications of Hsp90 and their contributions to chaperone regulation. Biochim Biophys Acta 1823:648–655

    Article  CAS  PubMed  Google Scholar 

  • Mostaghel EA, Page ST, Lin DW et al (2007) Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res 67:5033–5041

    Article  CAS  PubMed  Google Scholar 

  • Naruse K, Matsuura-Suzuki E, Watanabe M, Iwasaki S, Tomari Y (2018) In vitro reconstitution of chaperone-mediated human RISC assembly. RNA 24:6–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neckers L, Ivy SP (2003) Heat shock protein 90. Curr Opin Oncol 15:419–424

    Article  CAS  PubMed  Google Scholar 

  • Ni L, Yang CS, Gioeli D, Frierson H, Toft DO, Paschal BM (2010) FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells. Mol Cell Biol 30:1243–1253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palermo CM, Westlake CA, Gasiewicz TA (2005) Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein. Biochemistry 44:5041–5052

    Article  CAS  PubMed  Google Scholar 

  • Pan J, Jiang F, Zhou J, Wu D, Sheng Z, Li M (2018) HSP90: a novel target gene of miRNA-628-3p in A549 cells. Biomed Res Int 2018:1–10. ID:4149707. https://doi.org/10.1155/2018/4149707

    Article  CAS  Google Scholar 

  • Pearl LH, Prodromou C (2006) Structure and mechanism of the Hsp90 molecular chaperone machinery. Annu Rev Biochem 75:271–294

    Article  CAS  PubMed  Google Scholar 

  • Pei H, Li L, Fridley BL, Jenkins GD, Kalari KR, Lingle W, Petersen G, Lou Z, Wang L (2009) FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell 16:259–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pennisi R, Ascenzi P, di Masi A (2015) Hsp90: a new player in DNA repair? Biomol Ther 5:2589–2618

    CAS  Google Scholar 

  • Periyasamy S, Warrier M, Tillekeratne MP, Shou W, Sanchez ER (2007) The immunophilin ligands cyclosporin A and FK506 suppress prostate cancer cell growth by androgen receptor-dependent and -independent mechanisms. Endocrinology 148:4716–4726

    Article  CAS  PubMed  Google Scholar 

  • Periyasamy S, Hinds T Jr, Shemshedini L, Shou W, Sanchez ER (2010) FKBP51 and Cyp40 are positive regulators of androgen-dependent prostate cancer cell growth and the targets of FK506 and cyclosporin A. Oncogene 29:1691–1701

    Article  CAS  PubMed  Google Scholar 

  • Pratt WB (1997) The role of the hsp90-based chaperone system in signal transduction by nuclear receptors and receptors signaling via MAP kinase. Annu Rev Pharmacol Toxicol 37:297–326

    Article  CAS  PubMed  Google Scholar 

  • Pratt WB, Toft DO (1997) Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18:306–360

    CAS  PubMed  Google Scholar 

  • Pratt WB, Krishna P, Olsen LJ (2001) Hsp90-binding immunophilins in plants: the protein movers. Trends Plant Sci 6:54–58

    Article  CAS  PubMed  Google Scholar 

  • Prodromou C, Nuttall JM, Millson SH, Roe SM, Sim TS, Tan D, Workman P, Pearl LH, Piper PW (2009) Structural basis of the radicicol resistance displayed by a fungal hsp90. ACS Chem Biol 4:289–297

    Article  CAS  PubMed  Google Scholar 

  • Protti MP, Heltai S, Bellone M, Ferrarini M, Manfredi AA, Rugarli C (1994) Constitutive expression of the heat shock protein 72 kDa in human melanoma cells. Cancer Lett 85:211–216

    Article  CAS  PubMed  Google Scholar 

  • Queitsch C, Sangster TA, Lindquist S (2002) Hsp90 as a capacitor of phenotypic variation. Nature 417:618–624

    Article  CAS  PubMed  Google Scholar 

  • Quinta HR, Galigniana NM, Erlejman AG, Lagadari M, Piwien-Pilipuk G, Galigniana MD (2011) Management of cytoskeleton architecture by molecular chaperones and immunophilins. Cell Signal 23:1907–1920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramsey AJ, Russell LC, Chinkers M (2009) C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins. Biochem J 423:411–419

    Article  CAS  PubMed  Google Scholar 

  • Ratajczak T (2015) Steroid receptor-associated Immunophilins: candidates for diverse drug-targeting approaches in disease. Curr Mol Pharmacol 9:66–95

    Article  CAS  PubMed  Google Scholar 

  • Ratzke C, Mickler M, Hellenkamp B, Buchner J, Hugel T (2010) Dynamics of heat shock protein 90 C-terminal dimerization is an important part of its conformational cycle. Proc Natl Acad Sci U S A 107:16101–16106

    Article  PubMed  PubMed Central  Google Scholar 

  • Reikvam H, Ersvaer E, Bruserud O (2009) Heat shock protein 90 – a potential target in the treatment of human acute myelogenous leukemia. Curr Cancer Drug Targets 9:761–776

    Article  CAS  PubMed  Google Scholar 

  • Richter K, Haslbeck M, Buchner J (2010) The heat shock response: life on the verge of death. Mol Cell 40:253–266

    Article  CAS  PubMed  Google Scholar 

  • Romano S, D’Angelillo A, Pacelli R et al (2010) Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells. Cell Death Differ 17:145–157

    Article  CAS  PubMed  Google Scholar 

  • Rotoli D, Morales M, Del Carmen Maeso M, Del Pino Garcia M, Morales A, Avila J, Martin-Vasallo P (2016) Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy. Oncol Lett 12:1315–1322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rotoli D, Morales M, Avila J, Maeso M DC, Garcia MDP, Mobasheri A, Martin-Vasallo P (2017) Commitment of scaffold proteins in the onco-biology of human colorectal cancer and liver metastases after oxaliplatin-based chemotherapy. Int J Mol Sci 18, pii: E891.https://doi.org/10.3390/ijms18040891

  • Russo D, Merolla F, Mascolo M et al. (2017) FKBP51 immunohistochemical expression: a new prognostic biomarker for OSCC? Int J Mol Sci 18, pii: E443. https://doi.org/10.3390/ijms18020443

  • Rutherford SL, Lindquist S (1998) Hsp90 as a capacitor for morphological evolution. Nature 396:336–342

    Article  CAS  PubMed  Google Scholar 

  • Sahu B, Laakso M, Pihlajamaa P, Ovaska K, Sinielnikov I, Hautaniemi S, Janne OA (2013) FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells. Cancer Res 73:1570–1580

    Article  CAS  PubMed  Google Scholar 

  • Sangster TA, Salathia N, Lee HN et al (2008) HSP90-buffered genetic variation is common in Arabidopsis thaliana. Proc Natl Acad Sci U S A 105:2969–2974

    Article  PubMed  PubMed Central  Google Scholar 

  • Sarkar AA, Zohn IE (2012) Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme. J Cell Biol 196:789–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scammell JG, Denny WB, Valentine DL, Smith DF (2001) Overexpression of the FK506-binding immunophilin FKBP51 is the common cause of glucocorticoid resistance in three New World primates. Gen Comp Endocrinol 124:152–165

    Article  CAS  PubMed  Google Scholar 

  • Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I (2000) Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine. Cell 101:199–210

    Article  CAS  PubMed  Google Scholar 

  • Schulte TW, Neckers LM (1998) The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother Pharmacol 42:273–279

    Article  CAS  PubMed  Google Scholar 

  • Schulte TW, Akinaga S, Soga S, Sullivan W, Stensgard B, Toft D, Neckers LM (1998) Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 3:100–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schuster M, Schnell L, Feigl P et al (2017) The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells. Sci Rep 7:613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scroggins BT, Neckers L (2007) Post-translational modification of heat-shock protein 90: impact on chaperone. Expert Opin Drug Discovery 2:1403–1414

    Article  CAS  Google Scholar 

  • Shelton SN, Shawgo ME, Matthews SB et al (2009) KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock protein, exerts potent antiproliferative effects in human leukemic cells. Mol Pharmacol 76:1314–1322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Y, Liu X, Lou J, Han X, Zhang L, Wang Q, Li B, Dong M, Zhang Y (2014) Plasma levels of heat shock protein 90 alpha associated with lung cancer development and treatment responses. Clin Cancer Res 20:6016–6022

    Article  CAS  PubMed  Google Scholar 

  • Shimamura T, Lowell AM, Engelman JA, Shapiro GI (2005) Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins. Cancer Res 65:6401–6408

    Article  CAS  PubMed  Google Scholar 

  • Shore D, Bianchi A (2009) Telomere length regulation: coupling DNA end processing to feedback regulation of telomerase. EMBO J 28:2309–2322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sigal NH, Dumont FJ (1992) Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction. Annu Rev Immunol 10:519–560

    Article  CAS  PubMed  Google Scholar 

  • Solassol J, Mange A, Maudelonde T (2011) FKBP family proteins as promising new biomarkers for cancer. Curr Opin Pharmacol 11:320–325

    Article  CAS  PubMed  Google Scholar 

  • Solit DB, Chiosis G (2008) Development and application of Hsp90 inhibitors. Drug Discov Today 13:38–43

    Article  CAS  PubMed  Google Scholar 

  • Soti C, Racz A, Csermely P (2002) A nucleotide-dependent molecular switch controls ATP binding at the C-terminal domain of Hsp90. N-terminal nucleotide binding unmasks a C-terminal binding pocket. J Biol Chem 277:7066–7075

    Article  CAS  PubMed  Google Scholar 

  • Sreedhar AS, Soti C, Csermely P (2004) Inhibition of Hsp90: a new strategy for inhibiting protein kinases. Biochim Biophys Acta 1697:233–242

    Article  CAS  PubMed  Google Scholar 

  • Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP (1997) Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumour agent. Cell 89:239–250

    Article  CAS  PubMed  Google Scholar 

  • Storer CL, Dickey CA, Galigniana MD, Rein T, Cox MB (2011) FKBP51 and FKBP52 in signaling and disease. Trends Endocrinol Metab 22:481–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Supko JG, Hickman RL, Grever MR Malspeis L (1995) Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother Pharmacol 36:305–315

    Google Scholar 

  • Taipale M, Krykbaeva I, Koeva M, Kayatekin C, Westover KD, Karras GI, Lindquist S (2012) Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 150:987–1001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taipale M, Tucker G, Peng J et al (2014) A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 158:434–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taira T, Sawai M, Ikeda M, Tamai K, Iguchi-Ariga SM, Ariga H (1999) Cell cycle-dependent switch of up-and down-regulation of human hsp70 gene expression by interaction between c-Myc and CBF/NF-Y. J Biol Chem 274:24270–24279

    Article  CAS  PubMed  Google Scholar 

  • Tatro ET, Everall IP, Kaul M, Achim CL (2009) Modulation of glucocorticoid receptor nuclear translocation in neurons by immunophilins FKBP51 and FKBP52: implications for major depressive disorder. Brain Res 1286:1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng SC, Chen YY, Su YN, Chou PC, Chiang YC, Tseng SF, Wu KJ (2004) Direct activation of HSP90A transcription by c-Myc contributes to c-Myc-induced transformation. J Biol Chem 279:14649–14655

    Article  CAS  PubMed  Google Scholar 

  • Trepel J, Mollapour M, Giaccone G, Neckers L (2010) Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 10:537–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsutsumi S, Scroggins B, Koga F, Lee MJ, Trepel J, Felts S, Carreras C, Neckers L (2008) A small molecule cell-impermeant Hsp90 antagonist inhibits tumour cell motility and invasion. Oncogene 27:2478–2487

    Article  CAS  PubMed  Google Scholar 

  • Vafopoulou X, Steel CG (2012) Cytoplasmic travels of the ecdysteroid receptor in target cells: pathways for both genomic and non-genomic actions. Front Endocrinol 3:43. https://doi.org/10.3389/fendo.2012.00043

    Article  Google Scholar 

  • van Kouwenhove M, Kedde M, Agami R (2011) MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer 11:644–656

    Article  CAS  PubMed  Google Scholar 

  • Vandevyver S, Dejager L, Libert C (2012) On the trail of the glucocorticoid receptor: into the nucleus and back. Traffic 13:364–374

    Article  CAS  PubMed  Google Scholar 

  • Wang L (2011) FKBP51 regulation of AKT/protein kinase B phosphorylation. Curr Opin Pharmacol 11:360–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Kirschner A, Fabian AK et al (2013) Increasing the efficiency of ligands for FK506-binding protein 51 by conformational control. J Med Chem 56:3922–3935

    Article  CAS  PubMed  Google Scholar 

  • Ward BK, Mark PJ, Ingram DM, Minchin RF, Ratajczak T (1999) Expression of the estrogen receptor-associated immunophilins, cyclophilin 40 and FKBP52, in breast cancer. Breast Cancer Res Treat 58:267–280

    Article  CAS  PubMed  Google Scholar 

  • Wawrzynow B, Zylicz A, Zylicz M (2018) Chaperoning the guardian of the genome. The two-faced role of molecular chaperones in p53 tumour suppressor action. Biochim Biophys Acta Rev Cancer 1869:161–174

    Article  CAS  PubMed  Google Scholar 

  • Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM (1994) Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A 91:8324–8328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiederrecht GJ, Sabers CJ, Brunn GJ, Martin MM, Dumont FJ, Abraham RT (1995) Mechanism of action of rapamycin: new insights into the regulation of G1-phase progression in eukaryotic cells. Prog Cell Cycle Res 1:53–71

    Article  CAS  PubMed  Google Scholar 

  • Witkin SS (2001) Heat shock protein expression and immunity: relevance to gynecologic oncology. Eur J Gynaecol Oncol 22:249–256

    CAS  PubMed  Google Scholar 

  • Wochnik GM, Ruegg J, Abel GA, Schmidt U, Holsboer F, Rein T (2005) FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 280:4609–4616

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Liu T, Rios Z, Mei Q, Lin X, Cao S (2017) Heat shock proteins and cancer. Trends Pharmacol Sci 38:226–256

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Rao R, Shen J, Tang Y, Fiskus W, Nechtman J, Atadja P, Bhalla K (2008) Role of acetylation and extracellular location of heat shock protein 90alpha in tumour cell invasion. Cancer Res 68:4833–4842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yano M, Naito Z, Tanaka S, Asano G (1996) Expression and roles of heat shock proteins in human breast cancer. Japan J Cancer Res: Gann 87:908–915

    Article  CAS  Google Scholar 

  • Yu X, Harris SL, Levine AJ (2006) The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res 66:4795–4801

    Article  CAS  PubMed  Google Scholar 

  • Yufu Y, Nishimura J, Nawata H (1992) High constitutive expression of heat shock protein 90 alpha in human acute leukemia cells. Leuk Res 16:597–605

    Article  CAS  PubMed  Google Scholar 

  • Zhou H, Huang S (2010) mTOR signaling in cancer cell motility and tumour metastasis. Crit Rev Eukaryot Gene Expr 20:1–16

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The author acknowledges the financial support of the National Research Council of Argentina (CONICET), The University of Buenos Aires (UBACyT programme), and the National Agency for Scientific & Technological Programming (ANPCyT).

Author information

Authors and Affiliations

  1. Instituto de Biología y Medicina Experimental (IBYME)-CONICET & Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    Mario D. Galigniana

Authors
  1. Mario D. Galigniana
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mario D. Galigniana .

Editor information

Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Galigniana, M.D. (2019). HSP90-Based Heterocomplex as Essential Regulator for Cancer Disease. In: Asea, A., Kaur, P. (eds) Heat Shock Protein 90 in Human Diseases and Disorders. Heat Shock Proteins, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_2

Download citation

Publish with us

Policies and ethics

Search

Navigation