Advertisement

Hsp70 and Hsp27 as pharmacological targets in apoptosis modulation for cancer therapy

  • M. Brunet
  • C. Didelot
  • S. Subramaniam
  • A.L. Rérole
  • A. de Thonel
  • C. Garrido
Part of the Heat Shock Proteins book series (HESP, volume 2)

Abstract

The expression of heat shock proteins (HSP) HSP70 and HSP27 is induced in response to a wide variety of physiological and environmental insults including anticancer chemotherapy, thus allowing the cell to survive to lethal conditions. The cytoprotective effect of HSP70 and HSP27 is related to their ability to disable apoptosis. HSP70 and HSP27 both inhibit key apoptotic proteins at the pre- and post-mitochondrial level. HSP70 and/or HSP27 basal levels are unusually high in malignant cells, and both have been accused of participating in oncogenesis and/or in chemotherapy resistance. In rodent models, HSP70 or HSP27 over-expression increases tumor growth and metastatic potential. HSP70 and HSP27 depletion or inhibition frequently reduces the size of the tumors and even can cause their complete involution (for HSP70). In this chapter we will describe the effectors of the apoptotic machinery that interact with HSP70 or HSP27, and we will discuss the inhibition of HSP70 and HSP27 as a novel strategy of cancer therapy

Keywords

Heat shock proteins apoptosis cancer cell growth cancer cell esistance 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abe, M., Manola, J. B., Oh, W. K., Parslow, D. L., George, D. J., Austin, C. L., and Kantoff, P. W., 2004, Plasma levels of heat shock protein 70 in patients with prostate cancer: a potential biomarker for prostate cancer, Clin Prostate Cancer 3(1):49–53PubMedGoogle Scholar
  2. Arrigo, A. P., Virot, S., Chaufour, S., Firdaus, W., Kretz-Remy, C., and Diaz-Latoud, C., 2005, Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels, Antioxid Redox Signal 7(3–4):414–22PubMedGoogle Scholar
  3. Beckmann, R. P., Mizzen, L. E., and Welch, W. J., 1990, Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly, Science 248(4957):850–4PubMedGoogle Scholar
  4. Beere, H. M., Wolf, B. B., Cain, K., Mosser, D. D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R. I., Cohen, G. M., and Green, D. R., 2000, Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome, Nat Cell Biol 2(8):469–75PubMedGoogle Scholar
  5. Berrieman, H. K., Cawkwell, L., O’Kane, S. L., Smith, L., and Lind, M. J., 2006, Hsp27 may allow prediction of the response to single-agent vinorelbine chemotherapy in non-small cell lung cancer, Oncol Rep 15(1):283–6PubMedGoogle Scholar
  6. Biggs, W. H., 3rd, Meisenhelder, J., Hunter, T., Cavenee, W. K., and Arden, K. C., 1999, Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1, Proc Natl Acad Sci USA 96(13):7421–6PubMedGoogle Scholar
  7. Bivik, C., Rosdahl, I., and Ollinger, K., 2007, Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes, Carcinogenesis 28(3):537–44PubMedGoogle Scholar
  8. Brondani Da Rocha, A., Regner, A., Grivicich, I., Pretto Schunemann, D., Diel, C., Kovaleski, G., Brunetto De Farias, C., Mondadori, E., Almeida, L., Braga Filho, A., and Schwartsmann, G., 2004, Radioresistance is associated to increased Hsp70 content in human glioblastoma cell lines, Int J Oncol 25(3):777–85PubMedGoogle Scholar
  9. Bruey, J. M., Ducasse, C., Bonniaud, P., Ravagnan, L., Susin, S. A., Diaz-Latoud, C., Gurbuxani, S., Arrigo, A. P., Kroemer, G., Solary, E., and Garrido, C., 2000a, Hsp27 negatively regulates cell death by interacting with cytochrome c, Nat Cell Biol 2(9):645–52Google Scholar
  10. Bruey, J. M., Paul, C., Fromentin, A., Hilpert, S., Arrigo, A. P., Solary, E., and Garrido, C., 2000b, Differential regulation of HSP27 oligomerization in tumor cells grown in vitro and in vivo, Oncogene 19(42):4855–63Google Scholar
  11. Carrello, A., Allan, R. K., Morgan, S. L., Owen, B. A., Mok, D., Ward, B. K., Minchin, R. F., Toft, D. O., and Ratajczak, T., 2004, Interaction of the Hsp90 cochaperone cyclophilin 40 with Hsc70, Cell Stress Chaperones 9(2):167–81PubMedGoogle Scholar
  12. Casado, P., Zuazua-Villar, P., Valle, E. D., Martinez-Campa, C., Lazo, P. S., and Ramos, S., 2007, Vincristine regulates the phosphorylation of the antiapoptotic protein HSP27 in breast cancer cells, Cancer Lett 247(2):273–82PubMedGoogle Scholar
  13. Charette, S. J., Lavoie, J. N., Lambert, H., and Landry, J., 2000, Inhibition of Daxx-mediated apoptosis by heat shock protein 27, Mol Cell Biol 20(20):7602–12PubMedGoogle Scholar
  14. Chauhan, D., Li, G., Hideshima, T., Podar, K., Mitsiades, C., Mitsiades, N., Catley, L., Tai, Y. T., Hayashi, T., Shringarpure, R., Burger, R., Munshi, N., Ohtake, Y., Saxena, S., and Anderson, K. C., 2003a, Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance, Blood 102(9):3379–86Google Scholar
  15. Chauhan, D., Li, G., Shringarpure, R., Podar, K., Ohtake, Y., Hideshima, T., and Anderson, K. C., 2003b, Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells, Cancer Res 63(19):6174–7Google Scholar
  16. Ciocca, D. R., Oesterreich, S., Chamness, G. C., McGuire, W. L., and Fuqua, S. A., 1993, Biological and clinical implications of heat shock protein 27,000 (Hsp27): a review, J Natl Cancer Inst 85(19):1558–70PubMedGoogle Scholar
  17. Concannon, C. G., Orrenius, S., and Samali, A., 2001, Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c, Gene Expr 9(4-5):195–201PubMedGoogle Scholar
  18. Creagh, E. M., Carmody, R. J., and Cotter, T. G., 2000, Heat shock protein 70 inhibits caspase-dependent and -independent apoptosis in Jurkat T cells, Exp Cell Res 257(1):58–66PubMedGoogle Scholar
  19. Daugas, E., Susin, S. A., Zamzami, N., Ferri, K. F., Irinopoulou, T., Larochette, N., Prevost, M. C., Leber, B., Andrews, D., Penninger, J., and Kroemer, G., 2000, Mitochondrio-nuclear translocation of AIF in apoptosis and necrosis, Faseb J 14(5):729–39PubMedGoogle Scholar
  20. De, A. K., and Roach, S. E., 2004, Detection of the soluble heat shock protein 27 (hsp27) in human serum by an ELISA, J Immunoassay Immunochem 25(2):159–70PubMedGoogle Scholar
  21. De Los Rios, P., Ben-Zvi, A., Slutsky, O., Azem, A., and Goloubinoff, P., 2006, Hsp70 chaperones accelerate protein translocation and the unfolding of stable protein aggregates by entropic pulling, Proc Natl Acad Sci USA 103(16):6166–71Google Scholar
  22. Demidenko, Z. N., Vivo, C., Halicka, H. D., Li, C. J., Bhalla, K., Broude, E. V., and Blagosklonny, M. V., 2006, Pharmacological induction of Hsp70 protects apoptosis-prone cells from doxorubicin: comparison with caspase-inhibitor- and cycle-arrest-mediated cytoprotection, Cell Death Differ 13(9):1434–41PubMedGoogle Scholar
  23. Dix, D. J., Allen, J. W., Collins, B. W., Mori, C., Nakamura, N., Poorman-Allen, P., Goulding, E. H., and Eddy, E. M., 1996, Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility, Proc Natl Acad Sci USA 93(8):3264–8PubMedGoogle Scholar
  24. Dorion, S., and Landry, J., 2002, Activation of the mitogen-activated protein kinase pathways by heat shock, Cell Stress Chaperones 7(2):200–6PubMedGoogle Scholar
  25. Du, C., Fang, M., Li, Y., Li, L., and Wang, X., 2000, Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition, Cell 102(1):33–42PubMedGoogle Scholar
  26. Ebert, M. P., Schafer, C., Chen, J., Hoffmann, J., Gu, P., Kubisch, C., Carl-McGrath, S., Treiber, G., Malfertheiner, P., and Rocken, C., 2005, Protective role of heat shock protein 27 in gastric mucosal injury, J Pathol 207(2):177–84PubMedGoogle Scholar
  27. Ehrnsperger, M., Graber, S., Gaestel, M., and Buchner, J., 1997, Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation, Embo J 16(2):221–9PubMedGoogle Scholar
  28. Feng, J. T., Liu, Y. K., Song, H. Y., Dai, Z., Qin, L. X., Almofti, M. R., Fang, C. Y., Lu, H. J., Yang, P. Y., and Tang, Z. Y., 2005, Heat-shock protein 27: a potential biomarker for hepatocellular carcinoma identified by serum proteome analysis, Proteomics 5(17):4581–8PubMedGoogle Scholar
  29. Gabai, V. L., Yaglom, J. A., Volloch, V., Meriin, A. B., Force, T., Koutroumanis, M., Massie, B., Mosser, D. D., and Sherman, M. Y., 2000, Hsp72-mediated suppression of c-Jun N-terminal kinase is implicated in development of tolerance to caspase-independent cell death, Mol Cell Biol 20(18):6826–36PubMedGoogle Scholar
  30. Gao, T., and Newton, A. C., 2002, The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C, J Biol Chem 277(35):31585–92PubMedGoogle Scholar
  31. Garrido, C., 2002, Size matters: of the small HSP27 and its large oligomers, Cell Death Differ 9(5):483–5PubMedGoogle Scholar
  32. Garrido, C., Bruey, J. M., Fromentin, A., Hammann, A., Arrigo, A. P., and Solary, E., 1999, HSP27 inhibits cytochrome c-dependent activation of procaspase-9, Faseb J 13(14):2061–70PubMedGoogle Scholar
  33. Garrido, C., Fromentin, A., Bonnotte, B., Favre, N., Moutet, M., Arrigo, A. P., Mehlen, P., and Solary, E., 1998, Heat shock protein 27 enhances the tumorigenicity of immunogenic rat colon carcinoma cell clones, Cancer Res 58(23):5495–9PubMedGoogle Scholar
  34. Garrido, C., Gurbuxani, S., Ravagnan, L., and Kroemer, G., 2001, Heat shock proteins: endogenous modulators of apoptotic cell death, Biochem Biophys Res Commun 286(3):433–42PubMedGoogle Scholar
  35. Garrido, C., and Kroemer, G., 2004, Life’s smile, death’s grin: vital functions of apoptosis-executing proteins, Curr Opin Cell Biol 16(6):639–46PubMedGoogle Scholar
  36. Garrido, C., Mehlen, P., Fromentin, A., Hammann, A., Assem, M., Arrigo, A. P., and Chauffert, B., 1996, Inconstant association between 27-kDa heat-shock protein (Hsp27) content and doxorubicin resistance in human colon cancer cells. The doxorubicin-protecting effect of Hsp27, Eur J Biochem 237(3):653–9PubMedGoogle Scholar
  37. Garrido, C., Ottavi, P., Fromentin, A., Hammann, A., Arrigo, A. P., Chauffert, B., and Mehlen, P., 1997, HSP27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs, Cancer Res 57(13):2661–7PubMedGoogle Scholar
  38. Geisler, J. P., Tammela, J. E., Manahan, K. J., Geisler, H. E., Miller, G. A., Zhou, Z., and Wiemann, M. C., 2004, HSP27 in patients with ovarian carcinoma: still an independent prognostic indicator at 60 months follow-up, Eur J Gynaecol Oncol 25(2):165–8PubMedGoogle Scholar
  39. Gotz, R., Wiese, S., Takayama, S., Camarero, G. C., Rossoll, W., Schweizer, U., Troppmair, J., Jablonka, S., Holtmann, B., Reed, J. C., Rapp, U. R., and Sendtner, M., 2005, Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells, Nat Neurosci 8(9):1169–78PubMedGoogle Scholar
  40. Grossin, L., Cournil-Henrionnet, C., Pinzano, A., Gaborit, N., Dumas, D., Etienne, S., Stoltz, J. F., Terlain, B., Netter, P., Mir, L. M., and Gillet, P., 2006, Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis, Faseb J 20(1):65–75PubMedGoogle Scholar
  41. Guay, J., Lambert, H., Gingras-Breton, G., Lavoie, J. N., Huot, J., and Landry, J., 1997, Regulation of actin filament dynamics by p38 map kinase-mediated phosphorylation of heat shock protein 27, J Cell Sci 110 ( Pt 3):357–68PubMedGoogle Scholar
  42. Guo, F., Rocha, K., Bali, P., Pranpat, M., Fiskus, W., Boyapalle, S., Kumaraswamy, S., Balasis, M., Greedy, B., Armitage, E. S., Lawrence, N., and Bhalla, K., 2005a, Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin, Cancer Res 65(22):10536–44Google Scholar
  43. Guo, F., Sigua, C., Bali, P., George, P., Fiskus, W., Scuto, A., %Annavarapu, S., Mouttaki, A., Sondarva, G., Wei, S., Wu, J., Djeu, %J., and Bhalla, K., 2004, Mechanistic role of heat shock protein %70 in Bcr-Abl mediated resistance to apoptosis in human acute leukemia cells, Blood Google Scholar
  44. Guo, F., Sigua, C., Bali, P., George, P., Fiskus, W., Scuto, A., Annavarapu, S., Mouttaki, A., Sondarva, G., Wei, S., Wu, J., Djeu, J., and Bhalla, K., 2005b, Mechanistic role of heat shock protein 70 in Bcr-Abl-mediated resistance to apoptosis in human acute leukemia cells, Blood 105(5):1246–55Google Scholar
  45. Gurbuxani, S., Schmitt, E., Cande, C., Parcellier, A., Hammann, A., Daugas, E., Kouranti, I., Spahr, C., Pance, A., Kroemer, G., and Garrido, C., 2003, Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor, Oncogene 22(43):6669–78PubMedGoogle Scholar
  46. Gyrd-Hansen, M., Nylandsted, J., and Jaattela, M., 2004, Heat Shock Protein 70 Promotes Cancer Cell Viability by Safeguarding Lysosomal Integrity, Cell Cycle 3(12)Google Scholar
  47. Hoang, A. T., Huang, J., Rudra-Ganguly, N., Zheng, J., Powell, W. C., Rabindran, S. K., Wu, C., and Roy-Burman, P., 2000, A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma, Am J Pathol 156(3):857–64PubMedGoogle Scholar
  48. Hurlimann, J., Gebhard, S., and Gomez, F., 1993, Oestrogen receptor, progesterone receptor, pS2, ERD5, HSP27 and cathepsin D in invasive ductal breast carcinomas, Histopathology 23(3):239–48PubMedGoogle Scholar
  49. Jaattela, M., 1995, Over-expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells, Int J Cancer 60(5):689–93PubMedGoogle Scholar
  50. Jaattela, M., Wissing, D., Kokholm, K., Kallunki, T., and Egeblad, M., 1998, Hsp70 exerts its anti-apoptotic function downstream of caspase-3-like proteases, Embo J 17(21):6124–34PubMedGoogle Scholar
  51. Joo, M., Chi, J. G., and Lee, H., 2005, Expressions of HSP70 and HSP27 in hepatocellular carcinoma, J Korean Med Sci 20(5):829–34PubMedGoogle Scholar
  52. Joza, N., Susin, S. A., Daugas, E., Stanford, W. L., Cho, S. K., Li, C. Y., Sasaki, T., Elia, A. J., Cheng, H. Y., Ravagnan, L., Ferri, K. F., Zamzami, N., Wakeham, A., Hakem, R., Yoshida, H., Kong, Y. Y., Mak, T. W., Zuniga-Pflucker, J. C., Kroemer, G., and Penninger, J. M., 2001, Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death, Nature 410(6828):549–54Google Scholar
  53. Kalinowska, M., Garncarz, W., Pietrowska, M., Garrard, W. T., and Widlak, P., 2005, Regulation of the human apoptotic DNase/RNase Endonuclease G: involvement of Hsp70 and ATP, Apoptosis 10(4):821–30PubMedGoogle Scholar
  54. Kamal, A., Thao, L., Sensintaffar, J., Zhang, L., Boehm, M. F., Fritz, L. C., and Burrows, F. J., 2003, A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors, Nature 425(6956):407–10PubMedGoogle Scholar
  55. Komarova, E. Y., Afanasyeva, E. A., Bulatova, M. M., Cheetham, M. E., Margulis, B. A., and Guzhova, I. V., 2004, Downstream caspases are novel targets for the antiapoptotic activity of the molecular chaperone hsp70, Cell Stress Chaperones 9(3):265–75PubMedGoogle Scholar
  56. Kuo, C. C., Liang, S. M., and Liang, C. M., 2006, CpG-B ODN promotes cell survival via up-regulation of heat-shock protein 70 to increase BCL-XL and decrease apoptosis-inducing factor (AIF) translocation, J Biol Chem 281(50):38200–7PubMedGoogle Scholar
  57. Lee, J. H., Sun, D., Cho, K. J., Kim, M. S., Hong, M. H., Kim, I. K., and Lee, J. S., 2007, Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells confers chemoresistance associated with cell growth delay, J Cancer Res Clin Oncol 133(1):37–46PubMedGoogle Scholar
  58. Lee, J. S., Lee, J. J., and Seo, J. S., 2005a, 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(8):6634–41Google Scholar
  59. Lee, Y. J., Lee, D. H., Cho, C. K., Bae, S., Jhon, G. J., Lee, S. J., Soh, J. W., and Lee, Y. S., 2005b, HSP25 inhibits protein kinase C delta-mediated cell death through direct interaction, J Biol Chem 280(18):18108–19Google Scholar
  60. Lee, Y. J., Lee, D. H., Cho, C. K., Chung, H. Y., Bae, S., Jhon, G. J., Soh, J. W., Jeoung, D. I., Lee, S. J., and Lee, Y. S., 2005c, HSP25 inhibits radiation-induced apoptosis through reduction of PKCdelta-mediated ROS production, Oncogene 24(23):3715–25Google Scholar
  61. Lelj-Garolla, B., and Mauk, A. G., 2006, Self-association and chaperone activity of Hsp27 are thermally activated, J Biol Chem 281(12):8169–74PubMedGoogle Scholar
  62. Lemieux, P., Oesterreich, S., Lawrence, J. A., Steeg, P. S., Hilsenbeck, S. G., Harvey, J. M., and Fuqua, S. A., 1997, The small heat shock protein hsp27 increases invasiveness but decreases motility of breast cancer cells, Invasion Metastasis 17(3):113–23PubMedGoogle Scholar
  63. Li, C. Y., Lee, J. S., Ko, Y. G., Kim, J. I., and Seo, J. S., 2000, Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation, J Biol Chem 275(33):25665–71PubMedGoogle Scholar
  64. Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., and Wang, X., 1997, Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade, Cell 91(4):479–89PubMedGoogle Scholar
  65. Liu, Q. L., Kishi, H., Ohtsuka, K., and Muraguchi, A., 2003, Heat shock protein 70 binds caspase-activated DNase and enhances its activity in TCR-stimulated T cells, Blood 102(5):1788–96PubMedGoogle Scholar
  66. Lo Muzio, L., Campisi, G., Farina, A., Rubini, C., Ferrari, F., Falaschini, S., Leonardi, R., Carinci, F., Stalbano, S., and De Rosa, G., 2006, Prognostic value of HSP27 in head and neck squamous cell carcinoma: a retrospective analysis of 57 tumours, Anticancer Res 26(2B):1343-9PubMedGoogle Scholar
  67. Lo Muzio, L., Leonardi, R., Mariggio, M. A., Mignogna, M. D., Rubini, C., Vinella, A., Pannone, G., Giannetti, L., Serpico, R., Testa, N. F., De Rosa, G., and Staibano, S., 2004, HSP 27 as possible prognostic factor in patients with oral squamous cell carcinoma, Histol Histopathol 19(1):119–28PubMedGoogle Scholar
  68. Marin-Vinader, L., Shin, C., Onnekink, C., Manley, J. L., and Lubsen, N. H., 2006, Hsp27 enhances recovery of splicing as well as rephosphorylation of SRp38 after heat shock, Mol Biol Cell 17(2):886–94PubMedGoogle Scholar
  69. Matsumori, Y., Hong, S. M., Aoyama, K., Fan, Y., Kayama, T., Sheldon, R. A., Vexler, Z. S., Ferriero, D. M., Weinstein, P. R., and Liu, J., 2005, Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury, J Cereb Blood Flow Metab 25(7):899–910PubMedGoogle Scholar
  70. Mayer, M. P., and Bukau, B., 2005, Hsp70 chaperones: cellular functions and molecular mechanism, Cell Mol Life Sci 62(6):670–84PubMedGoogle Scholar
  71. Mehlen, P., Schulze-Osthoff, K., and Arrigo, A. P., 1996, Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death, J Biol Chem 271(28):16510–4PubMedGoogle Scholar
  72. Miyake, H., Muramaki, M., Kurahashi, T., Yamanaka, K., Hara, I., and Fujisawa, M., 2006, Enhanced expression of heat shock protein 27 following neoadjuvant hormonal therapy is associated with poor clinical outcome in patients undergoing radical prostatectomy for prostate cancer, Anticancer Res 26(2B):1583–7PubMedGoogle Scholar
  73. Mosser, D. D., Caron, A. W., Bourget, L., Meriin, A. B., Sherman, M. Y., Morimoto, R. I., and Massie, B., 2000, The chaperone function of hsp70 is required for protection against stress-induced apoptosis, Mol Cell Biol 20(19):7146–59PubMedGoogle Scholar
  74. Nakopoulou, L., Lazaris, A. C., Baltas, D., Giannopoulou, I., Kavantzas, N., and Tzonou, A., 1995, Prognostic evaluation of oestrogen-regulated protein immunoreactivity in ductal invasive (NOS) breast cancer, Virchows Arch 427(1):33–40PubMedGoogle Scholar
  75. Nanbu, K., Konishi, I., Mandai, M., Kuroda, H., Hamid, A. A., Komatsu, T., and Mori, T., 1998, Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas, Cancer Detect Prev 22(6):549–55PubMedGoogle Scholar
  76. Neckers, L., 2002, Hsp90 inhibitors as novel cancer chemotherapeutic agents, Trends Mol Med 8(4 Suppl):S55–61Google Scholar
  77. Neckers, L., and Ivy, S. P., 2003, Heat shock protein 90, Curr Opin Oncol 15(6):419–24PubMedGoogle Scholar
  78. Nollen, E. A., Brunsting, J. F., Roelofsen, H., Weber, L. A., and Kampinga, H. H., 1999, In vivo chaperone activity of heat shock protein 70 and thermotolerance, Mol Cell Biol 19(3):2069–79PubMedGoogle Scholar
  79. Nylandsted, J., Gyrd-Hansen, M., Danielewicz, A., Fehrenbacher, N., Lademann, U., Hoyer-Hansen, M., Weber, E., Multhoff, G., Rohde, M., and Jaattela, M., 2004, Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization, J Exp Med 200(4):425–35PubMedGoogle Scholar
  80. Nylandsted, J., Rohde, M., Brand, K., Bastholm, L., Elling, F., and Jaattela, M., 2000, Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2, Proc Natl Acad Sci USA 97(14):7871–6PubMedGoogle Scholar
  81. Oesterreich, S., Lee, A. V., Sullivan, T. M., Samuel, S. K., Davie, J. R., and Fuqua, S. A., 1997, Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells, J Cell Biochem 67(2):275–86PubMedGoogle Scholar
  82. Oya-Ito, T., Liu, B. F., and Nagaraj, R. H., 2006, Effect of methylglyoxal modification and phosphorylation on the chaperone and anti-apoptotic properties of heat shock protein 27, J Cell Biochem 99(1):279–91PubMedGoogle Scholar
  83. Ozes, O. N., Mayo, L. D., Gustin, J. A., Pfeffer, S. R., Pfeffer, L. M., and Donner, D. B., 1999, NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase, Nature 401(6748):82–5PubMedGoogle Scholar
  84. Pang, Q., Christianson, T. A., Keeble, W., Koretsky, T., and Bagby, G. C., 2002, The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC, J Biol Chem 277(51):49638–43PubMedGoogle Scholar
  85. Pang, Q., Keeble, W., Christianson, T. A., Faulkner, G. R., and Bagby, G. C., 2001, FANCC interacts with Hsp70 to protect hematopoietic cells from IFN-gamma/TNF-alpha-mediated cytotoxicity, Embo J 20(16):4478–89PubMedGoogle Scholar
  86. Parcellier, A., Brunet, M., Schmitt, E., Col, E., Didelot, C., Hammann, A., Nakayama, K., Nakayama, K. I., Khochbin, S., Solary, E., and Garrido, C., 2006, HSP27 favors ubiquitination and proteasomal degradation of p27Kip1 and helps S-phase re-entry in stressed cells, Faseb J 20(8):1179–81PubMedGoogle Scholar
  87. Parcellier, A., Gurbuxani, S., Schmitt, E., Solary, E., and Garrido, C., 2003a, Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways, Biochem Biophys Res Commun 304(3):505–12Google Scholar
  88. Parcellier, A., Schmitt, E., Brunet, M., Hammann, A., Solary, E., and Garrido, C., 2005, Small heat shock proteins HSP27 and alphaB-crystallin: cytoprotective and oncogenic functions, Antioxid Redox Signal 7(3–4):404–13PubMedGoogle Scholar
  89. Parcellier, A., Schmitt, E., Gurbuxani, S., Seigneurin-Berny, D., Pance, A., Chantome, A., Plenchette, S., Khochbin, S., Solary, E., and Garrido, C., 2003b, HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation, Mol Cell Biol 23(16):5790–802Google Scholar
  90. Park, H. S., Lee, J. S., Huh, S. H., Seo, J. S., and Choi, E. J., 2001, Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase, Embo J 20(3):446–56PubMedGoogle Scholar
  91. Paul, C., Manero, F., Gonin, S., Kretz-Remy, C., Virot, S., and Arrigo, A. P., 2002, Hsp27 as a negative regulator of cytochrome C release, Mol Cell Biol 22(3):816–34PubMedGoogle Scholar
  92. Rane, M. J., Pan, Y., Singh, S., Powell, D. W., Wu, R., Cummins, T., Chen, Q., McLeish, K. R., and Klein, J. B., 2003, Heat shock protein 27 controls apoptosis by regulating Akt activation, J Biol Chem 278(30):27828-35PubMedGoogle Scholar
  93. Ravagnan, L., Gurbuxani, S., Susin, S. A., Maisse, C., Daugas, E., Zamzami, N., Mak, T., Jaattela, M., Penninger, J. M., Garrido, C., and Kroemer, G., 2001, Heat-shock protein 70 antagonizes apoptosis-inducing factor, Nat Cell Biol 3(9):839–43PubMedGoogle Scholar
  94. Ray, S., Lu, Y., Kaufmann, S. H., Gustafson, W. C., Karp, J. E., Boldogh, I., Fields, A. P., and Brasier, A. R., 2004, Genomic mechanisms of p210BCR-ABL signaling: induction of heat shock protein 70 through the GATA response element confers resistance to paclitaxel-induced apoptosis, J Biol Chem 279(34):35604–15PubMedGoogle Scholar
  95. Ribeil, J. A., Zermati, Y., Vandekerkhove, J., Cathelin, S., Kersual, J., Dussiot, M., Coulon, S., Cruz Moura, I., Zeuner, A., Kirkegaard-Sörensen, T., Varet, B., Solary, E., Garrido, C., and Hermine, O., 2007, Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1, Nature 445(7123):102–5PubMedGoogle Scholar
  96. Rocchi, P., Beraldi, E., Ettinger, S., Fazli, L., Vessella, R. L., Nelson, C., and Gleave, M., 2005, Increased Hsp27 after androgen ablation facilitates androgen-independent progression in prostate cancer via signal transducers and activators of transcription 3-mediated suppression of apoptosis, Cancer Res 65(23):11083–93PubMedGoogle Scholar
  97. Rocchi, P., Jugpal, P., So, A., Sinneman, S., Ettinger, S., Fazli, L., Nelson, C., and Gleave, M., 2006, 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 Google Scholar
  98. Rocchi, P., So, A., Kojima, S., Signaevsky, M., Beraldi, E., Fazli, L., Hurtado-Coll, A., Yamanaka, K., and Gleave, M., 2004, Heat shock protein 27 increases after androgen ablation and plays a cytoprotective role in hormone-refractory prostate cancer, Cancer Res 64(18):6595–602PubMedGoogle Scholar
  99. Ruchalski, K., Mao, H., Li, Z., Wang, Z., Gillers, S., Wang, Y., Mosser, D. D., Gabai, V., Schwartz, J. H., and Borkan, S. C., 2006, Distinct hsp70 domains mediate apoptosis-inducing factor release and nuclear accumulation, J Biol Chem 281(12):7873–80PubMedGoogle Scholar
  100. Sakahira, H., and Nagata, S., 2002, Co-translational folding of caspase-activated DNase with Hsp70, Hsp40, and inhibitor of caspase-activated DNase, J Biol Chem 277(5):3364–70PubMedGoogle Scholar
  101. Sakamoto, H., Mashima, T., Yamamoto, K., and Tsuruo, T., 2002, Modulation of heat-shock protein 27 (Hsp27) anti-apoptotic activity by methylglyoxal modification, J Biol Chem 277(48):45770–5PubMedGoogle Scholar
  102. Santarosa, M., Favaro, D., Quaia, M., and Galligioni, E., 1997, Expression of heat shock protein 72 in renal cell carcinoma: possible role and prognostic implications in cancer patients, Eur J Cancer 33(6):873–7PubMedGoogle Scholar
  103. Sarto, C., Valsecchi, C., Magni, F., Tremolada, L., Arizzi, C., Cordani, N., Casellato, S., Doro, G., Favini, P., Perego, R. A., Raimondo, F., Ferrero, S., Mocarelli, P., and Galli-Kienle, M., 2004, Expression of heat shock protein 27 in human renal cell carcinoma, Proteomics 4(8):2252–60PubMedGoogle Scholar
  104. Schmitt, E., Maingret, L., Puig, P. E., Rerole, A. L., Ghiringhelli, F., Hammann, A., Solary, E., Kroemer, G., and Garrido, C., 2006, Heat shock protein 70 neutralization exerts potent antitumor effects in animal models of colon cancer and melanoma, Cancer Res 66(8):4191–7PubMedGoogle Scholar
  105. Schmitt, E., Parcellier, A., Gurbuxani, S., Cande, C., Hammann, A., Morales, M. C., Hunt, C. R., Dix, D. J., Kroemer, R. T., Giordanetto, F., Jaattela, M., Penninger, J. M., Pance, A., Kroemer, G., and Garrido, C., 2003, Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant, Cancer Res 63(23):8233–40PubMedGoogle Scholar
  106. Shashidharamurthy, R., Koteiche, H. A., Dong, J., and McHaourab, H. S., 2005, 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(7):5281–9PubMedGoogle Scholar
  107. Shi, Y., and Thomas, J. O., 1992, The transport of proteins into the nucleus requires the 70-kilodalton heat shock protein or its cytosolic cognate, Mol Cell Biol 12(5):2186–92PubMedGoogle Scholar
  108. Song, H., Ethier, S. P., Dziubinski, M. L., and Lin, J., 2004, Stat3 modulates heat shock 27kDa protein expression in breast epithelial cells, Biochem Biophys Res Commun 314(1):143–50PubMedGoogle Scholar
  109. Song, J., Takeda, M., and Morimoto, R. I., 2001, Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth, Nat Cell Biol 3(3):276–82PubMedGoogle Scholar
  110. Stankiewicz, A. R., Lachapelle, G., Foo, C. P., Radicioni, S. M., and Mosser, D. D., 2005, Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation, J Biol Chem 280(46):38729–39PubMedGoogle Scholar
  111. Steel, R., Doherty, J. P., Buzzard, K., Clemons, N., Hawkins, C. J., and Anderson, R. L., 2004, Hsp72 inhibits apoptosis upstream of the mitochondria and not through interactions with Apaf-1, J Biol Chem 279(49):51490–9PubMedGoogle Scholar
  112. Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., Brothers, G. M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., Larochette, N., Goodlett, D. R., Aebersold, R., Siderovski, D. P., Penninger, J. M., and Kroemer, G., 1999, Molecular characterization of mitochondrial apoptosis-inducing factor, Nature 397(6718):441–6PubMedGoogle Scholar
  113. Tanaka, Y., Fujiwara, K., Tanaka, H., Maehata, K., and Kohno, I., 2004, Paclitaxel inhibits expression of heat shock protein 27 in ovarian and uterine cancer cells, Int J Gynecol Cancer 14(4):616–20PubMedGoogle Scholar
  114. Teimourian, S., Jalal, R., Sohrabpour, M., and Goliaei, B., 2006, Down-regulation of Hsp27 radiosensitizes human prostate cancer cells, Int J Urol 13(9):1221–5PubMedGoogle Scholar
  115. Thanner, F., Sutterlin, M. W., Kapp, M., Rieger, L., Morr, A. K., Kristen, P., Dietl, J., Gassel, A. M., and Muller, T., 2005, Heat shock protein 27 is associated with decreased survival in node-negative breast cancer patients, Anticancer Res 25(3A):1649–53PubMedGoogle Scholar
  116. Theriault, J. R., Lambert, H., Chavez-Zobel, A. T., Charest, G., Lavigne, P., and Landry, J., 2004, Essential role of the NH2-terminal WD/EPF motif in the phosphorylation-activated protective function of mammalian Hsp27, J Biol Chem 279(22):23463–71PubMedGoogle Scholar
  117. Thomas, X., Campos, L., Mounier, C., Cornillon, J., Flandrin, P., Le, Q. H., Piselli, S., and Guyotat, D., 2005, Expression of heat-shock proteins is associated with major adverse prognostic factors in acute myeloid leukemia, Leuk Res 29(9):1049–58PubMedGoogle Scholar
  118. Tremolada, L., Magni, F., Valsecchi, C., Sarto, C., Mocarelli, P., Perego, R., Cordani, N., Favini, P., Galli Kienle, M., Sanchez, J. C., Hochstrasser, D. F., and Corthals, G. L., 2005, Characterization of heat shock protein 27 phosphorylation sites in renal cell carcinoma, Proteomics 5(3): 788–95Google Scholar
  119. Trieb, K., Lechleitner, T., Lang, S., Windhager, R., Kotz, R., and Dirnhofer, S., 1998, Heat shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy, Hum Pathol 29(10):1050–5PubMedGoogle Scholar
  120. van Heijst, J. W., Niessen, H. W., Musters, R. J., van Hinsbergh, V. W., Hoekman, K., and Schalkwijk, C. G., 2006, Argpyrimidine-modified Heat shock protein 27 in human non-small cell lung cancer: a possible mechanism for evasion of apoptosis, Cancer Lett 241(2):309–19PubMedGoogle Scholar
  121. Vargas-Roig, L. M., Gago, F. E., Tello, O., Aznar, J. C., and Ciocca, D. R., 1998, Heat shock protein expression and drug resistance in breast cancer patients treated with induction chemotherapy, Int J Cancer 79(5):468–75PubMedGoogle Scholar
  122. Vertii, A., Hakim, C., Kotlyarov, A., and Gaestel, M., 2006, Analysis of properties of small heat shock protein Hsp25 in MAPK-activated protein kinase 2 (MK2)-deficient cells: MK2-dependent insolubilization of Hsp25 oligomers correlates with susceptibility to stress, J Biol Chem 281(37):26966–75PubMedGoogle Scholar
  123. Wadhwa, R., Takano, S., Kaur, K., Deocaris, C. C., Pereira-Smith, O. M., Reddel, R. R., and Kaul, S. C., 2006, Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis, Int J Cancer 118(12):2973–80PubMedGoogle Scholar
  124. Wyttenbach, A., Sauvageot, O., Carmichael, J., Diaz-Latoud, C., Arrigo, A. P., and Rubinsztein, D. C., 2002, Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin, Hum Mol Genet 11(9):1137–51PubMedGoogle Scholar
  125. Xu, L., Chen, S., and Bergan, R. C., 2006, MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer, Oncogene 25(21):2987–98PubMedGoogle Scholar
  126. Yasuda, E., Kumada, T., Takai, S., Ishisaki, A., Noda, T., Matsushima-Nishiwaki, R., Yoshimi, N., Kato, K., Toyoda, H., Kaneoka, Y., Yamaguchi, A., and Kozawa, O., 2005, Attenuated phosphorylation of heat shock protein 27 correlates with tumor progression in patients with hepatocellular carcinoma, Biochem Biophys Res Commun 337(1):337–42PubMedGoogle Scholar
  127. Zermati, Y., Garrido, C., Amsellem, S., Fishelson, S., Bouscary, D., Valensi, F., Varet, B., Solary, E., and Hermine, O., 2001, Caspase activation is required for terminal erythroid differentiation, J Exp Med 193(2):247–54PubMedGoogle Scholar
  128. Zhao, Z. G., and Shen, W. L., 2005, Heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901, World J Gastroenterol 11(1):73–8PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • M. Brunet
    • 1
  • C. Didelot
    • 1
  • S. Subramaniam
    • 1
  • A.L. Rérole
    • 1
  • A. de Thonel
    • 1
  • C. Garrido
    • 1
  1. 1.INSERM UMR-866Faculty of Medicine and Pharmacy21039 DijonFrance

Personalised recommendations