HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review)

  • Authors:
    • Xiaoxia Wang
    • Meijuan Chen
    • Jing Zhou
    • Xu Zhang
  • View Affiliations

  • Published online on: April 25, 2014     https://doi.org/10.3892/ijo.2014.2399
  • Pages: 18-30
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Abstract

Among the heat shock proteins (HSP), HSP27, HSP70 and HSP90 are the most studied stress-inducible HSPs, and are induced in response to a wide variety of physiological and environmental insults, thus allowing cells to survive to lethal conditions based on their powerful cytoprotective functions. Different functions of HSPs have been described to explain their cytoprotective functions, including their most basic role as molecular chaperones, that is to regulate protein folding, transport, translocation and assembly, especially helping in the refolding of misfolded proteins, as well as their anti-apoptotic properties. In cancer cells, the expression and/or activity of the three HSPs is abnormally high, and is associated with increased tumorigenicity, metastatic potential of cancer cells and resistance to chemotherapy. Associating with key apoptotic factors, they are powerful anti-apoptotic proteins, having the capacity to block the cell death process at different levels. Altogether, the properties suggest that HSP27, HSP70 and HSP90 are appropriate targets for modulating cell death pathways. In this review, we summarize the role of HSP90, HSP70 and HSP27 in apoptosis and the emerging strategies that have been developed for cancer therapy based on the inhibition of the three HSPs.

References

1. 

Young JC, Agashe VR, Siegers K and Hartl FU: Pathways of chaperone-mediated protein folding in the cytosol. Nat Rev Mol Cell Biol. 5:781–791. 2004. View Article : Google Scholar : PubMed/NCBI

2. 

Lindquist S and Craig EA: The heat-shock proteins. Annu Rev Genet. 22:631–77. 1998. View Article : Google Scholar

3. 

Lebret T, Watson RW and Fitzpatrick JM: Heat shock proteins: their role in urological tumours. J Urolog. 169:338–346. 2003. View Article : Google Scholar : PubMed/NCBI

4. 

Khalil AA, Kabapy NF, Deraz SF and Smith C: Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets? Biochim Biophys Acta. 1816:89–104. 2011.PubMed/NCBI

5. 

Jego G, Hazoumé A, Seigneuric R and Garrido C: Targeting heat shock proteins in cancer. Cancer Lett. 332:275–285. 2013. View Article : Google Scholar : PubMed/NCBI

6. 

Xia Y, Rocchi P, Iovanna JL and Peng L: Targeting heat shock response pathways to treat pancreatic cancer. Drug Discov Today. 17:35–43. 2012. View Article : Google Scholar : PubMed/NCBI

7. 

Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E and Kroemer G: Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle. 5:2592–2601. 2006. View Article : Google Scholar : PubMed/NCBI

8. 

Joly AL, Wettstein G, Mignot G, Ghiringhelli F and Garrido C: Dual role of heat-shock proteins as regulator of apoptosis and innate immunity. J Innate Immun. 2:238–247. 2010. View Article : Google Scholar : PubMed/NCBI

9. 

Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB and Korsmeyer SJ: Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science. 292:727–30. 2001. View Article : Google Scholar : PubMed/NCBI

10. 

Zong WX, Lindsten T, Ross AJ, MacGregor GR and Thompson CB: BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 15:1481–1486. 2001. View Article : Google Scholar : PubMed/NCBI

11. 

Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C and Kroemer G: Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 13:1423–1433. 2006. View Article : Google Scholar : PubMed/NCBI

12. 

Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X: Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 91:479–489. 1997. View Article : Google Scholar : PubMed/NCBI

13. 

Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, Sasaki T, Elia AJ, Cheng HY, Ravagnan L, Ferri KF, Zamzami N, Wakeham A, Hakem R, Yoshida H, Kong YY, Mak TW, Zuniga-Pflucker JC, Kroemer G and Penninger JM: Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature. 410:549–554. 2001. View Article : Google Scholar : PubMed/NCBI

14. 

Du C, Fang M, Li Y, Li L and Wang X: Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell. 102:33–42. 2000. View Article : Google Scholar : PubMed/NCBI

15. 

Luo X, Budihardjo I, Zou H, Slaughter C and Wang X: Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 94:481–490. 1998. View Article : Google Scholar : PubMed/NCBI

16. 

Shamovsky I and Nudler E: New insights into the mechanism of heat shock response activation. Cell Mol Life Sci. 65:855–861. 2008. View Article : Google Scholar : PubMed/NCBI

17. 

Akerfelt M, Morimoto RI and Sistonen L: Heat shock factors: integrators of cell stress, developmentand lifespan. Nat Rev Mol Cell Biol. 11:545–555. 2010. View Article : Google Scholar : PubMed/NCBI

18. 

Green M, Schuetz TJ, Sullivan EK and Kingston RE: A heat-shock responsive domain of human HSF1 that regulates transcription activation domain function. Mol Cell Biol. 15:3354–3362. 1995.PubMed/NCBI

19. 

Sistonen L, Sarge KD and Morimoto RI: Human heat shock factors 1 and 2 are differentially activated and can synergistically induce hsp70 gene transcription. Mol Cell Biol. 14:2087–2099. 1994.PubMed/NCBI

20. 

Nakai A, Tanabe M, Kawazoe Y, Inazawa J, Morimoto RI and Nagata K: HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator. Mol Cell Biol. 17:469–481. 1997.PubMed/NCBI

21. 

Akerfelt M, Trouillet D, Mezger V and Sistonen L: Heat shock factors at a cross road between stress and development. Ann NY Acad Sci. 1113:15–27. 2007. View Article : Google Scholar : PubMed/NCBI

22. 

Abane R and Mezger V: Roles of heat shock factors in gameto-genesis and development. FEBS J. 277:4150–4172. 2010. View Article : Google Scholar : PubMed/NCBI

23. 

Whitesell L and Lindquist S: Inhibiting the transcription factor HSF1 as an anticancer strategy. Expert Opin Ther Targets. 13:469–478. 2009. View Article : Google Scholar : PubMed/NCBI

24. 

Westerheide SD, Kawahara TL, Orton K and Morimoto RI: Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death. J Biol Chem. 281:9616–9622. 2006. View Article : Google Scholar : PubMed/NCBI

25. 

Sugiyama Y, Suzuki A, Kishikawa M, Akutsu R, Hirose T and Waye MM: Muscle develops a specific form of small heat shock protein complex composed of MKBP/HSPB2 and HSPB3 during myogenic differentiation. J Biol Chem. 275:1095–1104. 2000. View Article : Google Scholar : PubMed/NCBI

26. 

Kostenko S and Moens U: Heat shock protein 27 phosphorylation: kinases, phosphatases, functions and pathology. Cell Mol Life Sci. 66:3289–3307. 2009. View Article : Google Scholar : PubMed/NCBI

27. 

Shin KD, Lee MY, Shin DS, Lee S, Son KH, Koh S, Paik YK, Kwon BM and Han DC: Blocking tumor cell migration and invasion with biphenyl isoxazole derivative KRIBB3, a synthetic molecule that inhibits Hsp27 phosphorylation. J Biol Chem. 280:41439–41448. 2005. View Article : Google Scholar : PubMed/NCBI

28. 

Gobbo J, Gaucher-Di-Stasio C, Weidmann S, Guzzo J and Garrido C: Quantification of HSP27 and HSP70 molecular chaperone activities. Methods Mol Biol. 787:137–143. 2011. View Article : Google Scholar : PubMed/NCBI

29. 

Bruey JM, Paul C, Fromentin A, Hilpert S, Arrigo AP, Solary E and Garrido C: Differential regulation of HSP27 oligomerization in tumor cells grown in vitro and in vivo. Oncogene. 19:4855–4863. 2000. View Article : Google Scholar : PubMed/NCBI

30. 

Shashidharamurthy R, Koteiche HA, Dong J and McHaourab HS: Mechanism of chaperone function in small heat shock proteins: Dissociation of the HSP27 oligomer is required for recognition and binding of destabilized T4 lysozyme. J Biol Chem. 280:5281–5289. 2005. View Article : Google Scholar : PubMed/NCBI

31. 

Charette SJ, Lavoie JN, Lambert H and Landry J: Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol. 20:7602–7612. 2000. View Article : Google Scholar : PubMed/NCBI

32. 

Akbar MT, Lundberg AM, Liu K, Vidyadaran S, Wells KE, Dolatshad H, Wynn S, Wells DJ, Latchman DS and de Belleroche J: The neuroprotective effects of heat shock protein 27 overexpression in transgenic animals against kainate-induced seizures and hippocampal cell death. J Biol Chem. 278:19956–19965. 2003. View Article : Google Scholar : PubMed/NCBI

33. 

Straume O, Shimamura T, Lampa MJ, Carretero J, Øyan AM, Jia D, Borgman CL and Soucheray M: Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer. Proc Natl Acad Sci USA. 109:8699–8704. 2012. View Article : Google Scholar : PubMed/NCBI

34. 

Bauer K, Nitsche U, Slotta-Huspenina J, Drecoll E, Von Weyhern CH, Rosenberg R, Höfler H and Langer R: High HSP27 and HSP70 expression levels are independent adverse prognostic factors in primary resected colon cancer. Cell Oncol (Dordr). 35:197–205. 2012. View Article : Google Scholar : PubMed/NCBI

35. 

Chen SF, Nieh S, Jao SW, Liu CL, Wu CH, Chang YC, Yang CY and Lin YS: Quercetin suppresses drug-resistant spheres via the p38 MAPK-Hsp27 apoptotic pathway in oral cancer cells. PLoS One. 7:e492752012. View Article : Google Scholar : PubMed/NCBI

36. 

Ciocca DR, Arrigo AP and Calderwood SK: Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update. Arch Toxicol. 87:19–48. 2013. View Article : Google Scholar : PubMed/NCBI

37. 

Pavan S, Musiani D, Torchiaro E, Migliardi G, Gai M, Di Cunto F, Erriquez J, Olivero M and Di Renzo MF: HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor. Int J Cancer. 134:1289–1299. 2013. View Article : Google Scholar : PubMed/NCBI

38. 

Acunzo J, Katsogiannou M and Rocchi P: Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. Int J Biochem Cell Biol. 44:1622–1631. 2012.

39. 

Schmitt E, Gehrmann M, Brunet M, Multhoff G and Garrido C: Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol. 81:15–27. 2007. View Article : Google Scholar : PubMed/NCBI

40. 

Voss OH, Batra S, Kolattukudy SJ, Gonzalez-Mejia ME, Smith JB and Doseff AI: Binding of caspase-3 prodomain to heat shock protein 27 regulates monocyte apoptosis by inhibiting caspase-3 proteolytic activation. J Biol Chem. 282:25088–25099. 2007. View Article : Google Scholar : PubMed/NCBI

41. 

Rocchi P, Jugpal P, So A, Sinneman S, Ettinger S, Fazli L, Nelson C and Gleave M: Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro. BJU Int. 98:1082–1089. 2006. View Article : Google Scholar : PubMed/NCBI

42. 

Paul C, Manero F, Gonin S, Kretz-Remy C, Virot S and Arrigo AP: Hsp27 as a negative regulator of cytochrome c release. Mol Cell Biol. 22:816–834. 2002. View Article : Google Scholar : PubMed/NCBI

43. 

Chauhan D, Li G, Hideshima T, Podar K, Mitsiades C, Mitsiades N, Catley L, Tai YT, Hayashi T, Shringarpure R, Burger R, Munshi N, Ohtake Y, Saxena S and Anderson KC: Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance. Blood. 102:3379–3386. 2003. View Article : Google Scholar : PubMed/NCBI

44. 

Havasi A, Li Z, Wang Z, Martin JL, Botla V and Ruchalski K: Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem. 283:12305–12313. 2008. View Article : Google Scholar : PubMed/NCBI

45. 

Arrigo AP, Virot S, Chaufour S, Firdaus W, Kretz-Remy C and Diaz-Latoud C: Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Signal. 7:414–422. 2005. View Article : Google Scholar

46. 

Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J and Gaestel M: Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. J Biol Chem. 274:18947–18956. 1999. View Article : Google Scholar

47. 

Sanchez-Niño MD, Sanz AB, Sanchez-Lopez E, Ruiz-Ortega M, Benito-Martin A, Saleem MA, Mathieson PW, Mezzano S, Egido J and Ortiz A: HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by highglucose and angiotensin II. Lab Invest. 92:32–45. 2012.

48. 

Solary E, Droin N, Bettaieb A, Corcos L, Dimanche-Boitrel MT and Garrido C: Positive and negative regulation of apoptotic pathways by cytotoxic agents in hematological malignancies. Leukemia. 14:1833–1849. 2000. View Article : Google Scholar : PubMed/NCBI

49. 

Kamada M, So A, Muramaki M, Rocchi P, Beraldi E and Gleave M: Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells. Mol Cancer Ther. 6:299–308. 2007. View Article : Google Scholar

50. 

Heinrich JC, Tuukkanen A, Schroeder M, Fahrig T and Fahrig R: RP101 (brivudine) binds to heat shock protein HSP27 (HSPB1) and enhances survival in animals and pancreatic cancer patients. J Cancer Res Clin Oncol. 137:1349–1361. 2011. View Article : Google Scholar : PubMed/NCBI

51. 

Seigneuric R, Gobbo J, Colas P and Garrido C: Targeting cancer with peptide aptamers. Oncotarget. 2:557–561. 2011.PubMed/NCBI

52. 

Gibert B, Hadchity E, Czekalla A, Aloy MT, Colas P, Rodriguez-Lafrasse C, Arrigo AP and Diaz-Latoud C: Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers. Oncogene. 30:3672–81. 2011. View Article : Google Scholar : PubMed/NCBI

53. 

Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B and Hightower LE: Hightower, Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones. 14:105–111. 2009. View Article : Google Scholar : PubMed/NCBI

54. 

Jäättelä M: Heat shock proteins as cellular lifeguards. Ann Med. 31:261–271. 1999.

55. 

Beckmann RP, Mizzen LE and Welch WJ: Interaction of Hsp 70 with newly synthesized proteins: Implications for protein folding and assembly. Science. 248:850–854. 1990. View Article : Google Scholar : PubMed/NCBI

56. 

Murakami H, Pain D and Blobel G: 70-kD heat shock-related protein is one of at least two distinct cytosolic factors stimulating protein import into mitochondria. J Cell Biol. 107:2051–2057. 1988. View Article : Google Scholar : PubMed/NCBI

57. 

Shi Y and Thomas JO: The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate. Mol Cell Biol. 12:2186–2192. 1992.PubMed/NCBI

58. 

Nollen EA, Brunsting JF, Roelofsen H, Weber LA and Kampinga HH: In vivo chaperone activity of heat shock protein 70 and thermotolerance. Mol Cell Biol. 19:2069–2079. 1999.PubMed/NCBI

59. 

Vogel M, Bukau B and Mayer MP: Allosteric regulation of Hsp70 chaperones by a proline switch. Mol Cell. 21:359–367. 2006. View Article : Google Scholar : PubMed/NCBI

60. 

Goloudina AR, Demidov ON and Garrido C: Inhibition of HSP70: a challenging anti-cancer strategy. Cancer Lett. 325:117–124. 2012. View Article : Google Scholar : PubMed/NCBI

61. 

Bukau B, Weissman J and Horwich A: Molecular chaperones and protein quality control. Cell. 125:443–451. 2006. View Article : Google Scholar : PubMed/NCBI

62. 

Schmitt E, Parcellier A, Gurbuxani S, Cande C, Hammann A, Morales MC, Hunt CR, Dix DJ, Kroemer RT, Giordanetto F, Jäättelä M, Penninger JM, Pance A, Kroemer G and Garrido C: Chemosensitization by a non-apoptogenic heat-shock protein 70-binding apoptosis-inducing factor mutant. Cancer Res. 63:8233–8240. 2003.PubMed/NCBI

63. 

Dix DJ, Allen JW, Collins BW, Mori C, Nakamura N, Poorman-Allen P, Goulding EH and Eddy EM: Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proc Natl Acad Sci USA. 93:3264–3268. 1996. View Article : Google Scholar : PubMed/NCBI

64. 

Johnson TR, Stone K and Nikrad M: The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells. Oncogene. 22:4953–4963. 2003. View Article : Google Scholar : PubMed/NCBI

65. 

Hui-qing X, Jian-da Z, Xin-min N, Yan-zhong Z, Cheng-qun L, Quan-yong H, Yi X, Pokharel PB, Shao-hua W and Dan X: HSP70 inhibits burn serum-induced apoptosis of cardiomyocytes via mitochondrial and membrane death receptor pathways. J Burn Care Res. 29:512–518. 2008. View Article : Google Scholar : PubMed/NCBI

66. 

Park HS, Cho SG, Kim CK, Hwang HS, Noh KT, Kim MS, Huh SH, Kim MJ, Ryoo K, Kim EK, Kang WJ, Lee JS, Seo JS, Ko YG, Kim S and Choi EJ: Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1. Mol Cell Biol. 22:7721–7730. 2002. View Article : Google Scholar : PubMed/NCBI

67. 

Park HS, Lee JS, Huh SH, Seo JS and Choi EJ: Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO J. 20:446–456. 2001. View Article : Google Scholar : PubMed/NCBI

68. 

Lee JS, Lee JJ and Seo JS: HSP70 deficiency results in activation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and caspase-3 in hyperosmolarity-induced apoptosis. J Biol Chem. 280:6634–6641. 2005. View Article : Google Scholar : PubMed/NCBI

69. 

Gao T and Newton AC: The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C. J Biol Chem. 277:31585–31592. 2002. View Article : Google Scholar : PubMed/NCBI

70. 

Zylicz M, King FW and Wawrzynow A: Hsp70 interactions with the p53 tumour suppressor protein. EMBO J. 20:4634–4638. 2001. View Article : Google Scholar : PubMed/NCBI

71. 

Yang X, Wang J, Zhou Y, Wang Y, Wang S and Zhang W: Hsp70 promotes chemoresistance by blocking Bax mitochondrial translocation in ovariancancer cells. Cancer Lett. 321:137–143. 2012. View Article : Google Scholar : PubMed/NCBI

72. 

Stankiewicz AR, Lachapelle G, Foo CP, Radicioni SM and Mosser DD: Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. J Biol Chem. 280:38729–38739. 2005. View Article : Google Scholar : PubMed/NCBI

73. 

Li CY, Lee JS, Ko YG, Kim JI and Seo JS: Heat shock protein 70 inhibits apoptosis down-stream of cytochrome c release and upstream of caspase-3 activation. J Biol Chem. 275:25665–25671. 2000. View Article : Google Scholar : PubMed/NCBI

74. 

Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM and Green DR: Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol. 2:469–475. 2000. View Article : Google Scholar : PubMed/NCBI

75. 

Creagh EM, Carmody RJ and Cotter TG: Heat shock protein 70 inhibits caspase-dependent and-independent apoptosis in Jurkat T cells. Exp Cell Res. 257:58–66. 2000. View Article : Google Scholar : PubMed/NCBI

76. 

Ravagnan L, Gurbuxani S, Susin SA, Maisse C, Daugas E, Zamzami N, Mak T, Jaattela M, Penninger JM, Garrido C and Kroemer G: Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol. 3:839–843. 2001. View Article : Google Scholar : PubMed/NCBI

77. 

Gurbuxani S, Schmitt E, Cande C, Parcellier A, Hammann A, Daugas E, Kouranti I, Spahr C, Pance A, Kroemer G and Garrido C: Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor. Oncogene. 22:6669–6678. 2003. View Article : Google Scholar : PubMed/NCBI

78. 

Matsumori Y, Hong SM, Aoyama K, Fan Y, Kayama T, Sheldon RA, Vexler ZS, Ferriero DM, Weinstein PR and Liu J: Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury. J Cereb Blood Flow Metab. 25:899–910. 2005. View Article : Google Scholar : PubMed/NCBI

79. 

Kalinowska M, Garncarz W, Pietrowska M, Garrard WT and Widlak P: Regulation of the human apoptotic DNase/RNase endonuclease G: Involvement of Hsp70 and ATP. Apoptosis. 10:821–830. 2005. View Article : Google Scholar : PubMed/NCBI

80. 

Sakahira H and Nagata S: Cotranslational folding of caspase-activated DNase with Hsp70, Hsp40, and inhibitor of caspase-activated DNase. J Biol Chem. 277:3364–3370. 2002. View Article : Google Scholar : PubMed/NCBI

81. 

Liu QL, Kishi H, Ohtsuka K and Muraguchi A: Heat shock protein 70 binds caspase-activated DNase and enhances its activity in TCR-stimulated T cells. Blood. 102:1788–1796. 2003. View Article : Google Scholar : PubMed/NCBI

82. 

Ribeil JA, Zermati Y, Vandekerckhove J, Cathelin S, Kersual J, Dussiot M, Coulon S, Moura IC, Zeuner A, Kirkegaard-Sørensen T, Varet B, Solary E, Garrido C and Hermine O: Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1. Nature. 445:102–105. 2007. View Article : Google Scholar

83. 

Gyrd-Hansen M, Nylandsted J and Jaattela M: Heat shock protein 70 promotes cancer cell viability by safeguarding lysosomal integrity. Cell Cycle. 3:1484–1485. 2004. View Article : Google Scholar : PubMed/NCBI

84. 

Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Hoyer-Hansen M, Weber E, Multhoff G, Rohde M and Jaattela M: Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med. 200:425–435. 2004. View Article : Google Scholar : PubMed/NCBI

85. 

Leu JI, Pimkina J, Frank A, Murphy ME and George DL: A small molecule inhibitor of inducible heat shock protein 70. Mol Cell. 36:15–27. 2009. View Article : Google Scholar : PubMed/NCBI

86. 

Schmitt E, Maingret L, Puig PE, Rerole AL, Ghiringhelli F, Hammann A, Solary E, Kroemer G and Garrido C: Heat-shock protein 70 neutralization exerts potent antitumor effects in animal models of colon cancer and melanoma. Cancer Res. 66:4191–4197. 2006. View Article : Google Scholar : PubMed/NCBI

87. 

Nadeau K, Nadler SG, Saulnier M, Tepper MA and Walsh CT: Quantitation of the interaction of the immunosuppressant deoxyspergualin and analogs with Hsc70 and Hsp90. Biochemistry. 33:2561–2567. 1994. View Article : Google Scholar : PubMed/NCBI

88. 

Fewell SW, Day BW and Brodsky JL: Identification of an inhibitor of hsc70-mediated protein translocation and ATP hydrolysis. J Biol Chem. 276:910–914. 2001. View Article : Google Scholar

89. 

Rodina A, Vilenchik M, Moulick K, Aguirre J, Kim J, Chiang A, Litz J, Clement CC, Kang Y, She Y, Wu N, Felts S, Wipf P, Massague J, Jiang X, Brodsky JL, Krystal GW and Chiosis G: Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nat Chem Biol. 3:498–507. 2007. View Article : Google Scholar : PubMed/NCBI

90. 

Wright CM, Seguin SP, Fewell SW, Zhang H, Ishwad C, Vats A, Lingwood CA, Wipf P, Fanning E, Pipas JM and Brodsky JL: Inhibition of SimianVirus 40 replication by targeting the molecular chaperone function and ATPase activity of T antigen. Virus Res. 141:71–80. 2009. View Article : Google Scholar : PubMed/NCBI

91. 

Massey AJ, Williamson DS, Browne H, Murray JB, Dokurno P, Shaw T, Macias AT, Daniels Z, Geoffroy S, Dopson M, Lavan P, Matassova N, Francis GL, Graham CJ, Parsons R, Wang Y, Padfield A, Comer M, Drysdale MJ and Wood M: A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 66:535–545. 2010. View Article : Google Scholar : PubMed/NCBI

92. 

Jinwal UK, Miyata Y, Koren J III, Jones JR, Trotter JH, Chang L, O’Leary J, Morgan D, Lee DC, Shults CL, Rousaki A, Weeber EJ, Zuiderweg ER, Gestwicki JE and Dickey CA: Chemical manipulation of hsp70 ATPase activity regulates tau stability. J Neurosci. 29:12079–88. 2009. View Article : Google Scholar : PubMed/NCBI

93. 

Wadhwa R, Sugihara T, Yoshida A, Nomura H, Reddel RR, Simpson R, Maruta H and Kaul SC: Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function. Cancer Res. 60:6818–6821. 2000.PubMed/NCBI

94. 

Wadhwa R, Yaguchi T, Hasan MK, Mitsui Y, Reddel RR and Kaul SC: Hsp70 family member, mot-2/mthsp70/GRP75, binds to the cytoplasmic sequestration domain of the p53 protein. Exp Cell Res. 274:246–253. 2002. View Article : Google Scholar : PubMed/NCBI

95. 

Britten CD, Rowinsky EK, Baker SD, Weiss GR, Smith L, Stephenson J, Rothenberg M, Smetzer L, Cramer J, Collins W, Von Hoff DD and Eckhardt SG: A phase I and pharmacokinetic study of the mitochondrial-specific rhodacyanine dye analog MKT 077. Clin Cancer Res. 6:42–49. 2000.PubMed/NCBI

96. 

Williams DR, Ko SK, Park S, Lee MR and Shin I: An apoptosis-inducing small molecule that binds to heat shock protein 70. Angew Chem Int Ed Engl. 47:7466–7469. 2008. View Article : Google Scholar : PubMed/NCBI

97. 

Powers MV, Jones K, Barillari C, Westwood I, van Montfort RL and Workman P: Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle. 9:1542–1550. 2010. View Article : Google Scholar : PubMed/NCBI

98. 

Whetstone H and Lingwood C: 3’Sulfogalactolipid binding specifically inhibits Hsp70 ATPase activity in vitro. Biochemistry. 42:1611–1617. 2003.

99. 

Chatterjee M, Andrulis M, Stühmer T, Müller E, Hofmann C, Steinbrunn T, Heimberger T, Schraud H, Kressmann S, Einsele H and Bargou RC: The PI3K/Akt signaling pathway regulates the expression of Hsp70, which critically contributes to Hsp90-chaperone function and tumor cell survival in multiple myeloma. Haematologica. 98:1132–1141. 2013. View Article : Google Scholar

100. 

Multhoff G and Radons J: Radiation, inflammation, and immune responses in cancer. Front Oncol. 2:582012. View Article : Google Scholar : PubMed/NCBI

101. 

Stangl S, Gehrmann M, Riegger J, Kuhs K, Riederer I, Sievert W, Hube K, Mocikat R, Dressel R, Kremmer E, Pockley AG, Friedrich L, Vigh L, Skerra A and Multhoff G: Targeting membrane heat-shock protein 70 (Hsp70) on tumors by cmHsp70.1 antibody. Proc Nat Acad Sci USA. 108:733–738. 2011. View Article : Google Scholar : PubMed/NCBI

102. 

Krause SW, Gastpar R, Andreesen R, Gross C, Ullrich H, Thonigs G, Pfister K and Multhoff G: Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase I trial. Clin Cancer Res. 10:3699–3707. 2004. View Article : Google Scholar : PubMed/NCBI

103. 

Whitesell L and Lindquist SL: HSP90 and the chaperoning of cancer. Nat Rev Cancer. 5:761–772. 2005. View Article : Google Scholar : PubMed/NCBI

104. 

Taipale M, Jarosz DF and Lindquist S: HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol. 11:515–528. 2010. View Article : Google Scholar : PubMed/NCBI

105. 

Sreedhar AS, Kalmár E, Csermely P and Shen YF: Hsp90 isoforms: functions, expression and clinical importance. FEBS Lett. 562:11–15. 2004. View Article : Google Scholar : PubMed/NCBI

106. 

Hartl FU, Bracher A and Hayer-Hartl M: Molecular chaperones in protein folding and proteostasis. Nature. 475:324–332. 2011. View Article : Google Scholar : PubMed/NCBI

107. 

Onuoha SC, Coulstock ET, Grossmann JG and Jackson SE: Structural studies on the co-chaperone Hop and its complexes with Hsp90. J Mol Biol. 379:732–744. 2008. View Article : Google Scholar : PubMed/NCBI

108. 

Mayer MP: Gymnastics of molecular chaperones. Mol Cell. 39:321–331. 2010. View Article : Google Scholar : PubMed/NCBI

109. 

Krukenberg KA, Street TO, Lavery LA and Agard DA: Conformational dynamics of the molecular chaperone Hsp90. Q Rev Biophys. 44:229–255. 2011. View Article : Google Scholar : PubMed/NCBI

110. 

Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B and Piper PW: Crysta l structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature. 440:1013–1017. 2006. View Article : Google Scholar : PubMed/NCBI

111. 

Normant E, Paez G and West KA: The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models. Oncogene. 30:2581–2586. 2011. View Article : Google Scholar : PubMed/NCBI

112. 

Neckers L and Workman P: HSP90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res. 18:64–76. 2012. View Article : Google Scholar : PubMed/NCBI

113. 

Modi S, Stopeck A and Linden H: HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res. 17:5132–5139. 2011. View Article : Google Scholar : PubMed/NCBI

114. 

Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

115. 

Khong T and Spencer A: Targeting HSP 90 induces apoptosis and inhibits critical survival and proliferation pathways in multiple myeloma. Mol Cancer Ther. 10:1909–1917. 2011. View Article : Google Scholar : PubMed/NCBI

116. 

Workman P, Burrows F, Neckers L and Rosen N: Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann NY Acad Sci. 1113:202–216. 2007. View Article : Google Scholar : PubMed/NCBI

117. 

Hartl FU: Chaperone-assisted protein folding: the path to discovery from a personal perspective. Nat Med. 17:1206–1210. 2011. View Article : Google Scholar : PubMed/NCBI

118. 

Tiroli-Cepeda AO and Ramos CH: An overview of the role of molecular chaperones in protein homeostasis. Protein Pept Lett. 18:101–109. 2011. View Article : Google Scholar : PubMed/NCBI

119. 

Patel HJ, Modi S, Chiosis G and Taldone T: Advances in the discovery and development of heat-shock protein 90 inhibitors for cancer treatment. Expert Opin Drug Discov. 6:559–587. 2011. View Article : Google Scholar : PubMed/NCBI

120. 

Sequist LV, Gettinger S and Natale R: A phase II trial of IPI-504 (retaspimycin hydrochloride), a novel Hsp90 inhibitor, in patients with relapsed and/or refractory stage IIIb or stage IV non-small cell lung cancer (NSCLC) stratified by EGFR mutation status. J Clin Oncol. 27:15s2009.

121. 

McCollum AK, Teneyck CJ, Sauer BM, Toft DO and Erlichman C: Up-regulation of heat shock protein 27 induces resistance to 17-allylamino-demethoxy geldanamycin through a glutathione-mediated mechanism. Cancer Res. 66:10967–10975. 2006. View Article : Google Scholar : PubMed/NCBI

122. 

Didelot C, Lanneau D, Brunet M, Bouchot A, Cartier J, Jacquel A, Ducoroy P, Cathelin S, Decologne N, Chiosis G, Dubrez-Daloz L, Solary E and Garrido C: Interaction of heat-shock protein 90 beta isoform (HSP90 beta) with cellular inhibitor of apoptosis 1 (c-IAP1) is required for cell differentiation. Cell Death Differ. 15:859–866. 2008. View Article : Google Scholar

123. 

Eustace BK, Sakurai T, Stewart JK, Yimlamai D, Unger C, Zehetmeier C, Lain B, Torella C, Henning SW, Beste G, Scroggins BT, Neckers L, Ilag LL and Jay DG: Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Nat Cell Biol. 6:507–514. 2004. View Article : Google Scholar : PubMed/NCBI

124. 

Wang X, Song X, Zhuo W, Fu Y, Shi H, Liang Y, Tong M, Chang G and Luo Y: The regulatory mechanism of Hsp90 alpha secretion and its function in tumor malignancy. Proc Natl Acad Sci USA. 106:21288–21293. 2009. View Article : Google Scholar : PubMed/NCBI

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July 2014
Volume 45 Issue 1

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APA
Wang, X., Chen, M., Zhou, J., & Zhang, X. (2014). HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review). International Journal of Oncology, 45, 18-30. https://doi.org/10.3892/ijo.2014.2399
MLA
Wang, X., Chen, M., Zhou, J., Zhang, X."HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review)". International Journal of Oncology 45.1 (2014): 18-30.
Chicago
Wang, X., Chen, M., Zhou, J., Zhang, X."HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review)". International Journal of Oncology 45, no. 1 (2014): 18-30. https://doi.org/10.3892/ijo.2014.2399