Skip to main content
SpringerLink
Log in
Book cover

Heat Shock Proteins in Cancer pp 73–92Cite as

Anti-apoptotic, Tumorigenic and Metastatic Potential of Hsp27 (HspB1) and αB-crystallin (HspB5): Emerging Targets for the Development of New Anti-Cancer Therapeutic Strategies

  • Chapter

Part of the book series: Heat Shock Proteins ((HESP,volume 2))

Abstract

Human Hsp27 (also denoted HspB1) and αB-crystallin (also denoted HspB5) are major heat-inducible small heat shock proteins (sHsps). These polypeptides share dynamic phosphorylation and oligomeric properties suggesting that different functional forms of these proteins exist. Elevated levels of expression of these sHsps counteract both necrotic and apoptotic cell deaths induced by various stimuli including heat shock, oxidative stress, inflammatory cytokines, death-receptor agonists and apoptotic inducers. In cells exposed to agents or conditions that unfold proteins, such as heat shock, these proteins act as ATP-independent molecular chaperones that can, in concert with other members of the heat shock protein family (i.e. Hsp70, Hsp40 and Hsp90), facilitate the repair or promote the degradation of damaged proteins which are potentially produced in stressed cells. In addition, Hsp27 and αB-crystallin limit the formation of oxidized macromolecules by stimulating the anti-oxidant defences of cell. Hsp27 and αB-crystallin also negatively regulate apoptosis through their ability to interact with several key components of the apoptotic signalling pathway. Moreover, particular oligomeric forms of these polypeptides stabilize the cytoskeleton. The high level of constitutive expression of Hsp27 and αB-crystallin in a wide range of tumors resistant to cancer therapeutics as well as their tumorigenic and metastatic potential designate these proteins as potential targets for future anti-cancer therapeutic strategies

This is a preview of subscription content, 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   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aoyama, A., Steiger, R., Frohli, E., Schafer, R., von Deimling, A., Wiestler, O., Klemenz, R., 1993. Expression of alpha B-crystallin in human brain tumors. Int J Cancer 55, 760–764.

    Article  PubMed  CAS  Google Scholar 

  • Arrigo, A.-P., 1995. Expression of stress genes during development. Neuropathol. and Applied Neurobiol. 21, 488–491.

    CAS  Google Scholar 

  • Arrigo, A.-P., Landry, J., 1994. Expression and Function of the Low-molecular-weight Heat Shock Proteins, In: Morimoto, R.I., Tissieres, A., Georgopoulos, C. (Eds.), In: The Biology of Heat Shock Proteins and Molecular Chaperones, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 335–373.

    Google Scholar 

  • Arrigo, A.-P., Suhan, J.P., Welch, W.J., 1988. Dynamic changes in the structure and intracellular locale of the mammalian low-molecular-weight heat shock protein. Mol. Cell. Biol. 8, 5059–5071.

    PubMed  CAS  Google Scholar 

  • Arrigo, A.P., 1998. Small stress proteins: chaperones that act as regulators of intracellular redox state and programmed cell death. Biol Chem 379, 19–26.

    PubMed  CAS  Google Scholar 

  • Arrigo, A.P., 2000. sHsp as novel regulators of programmed cell death and tumorigenicity. Pathol Biol (Paris) 48, 280–288.

    CAS  Google Scholar 

  • Arrigo, A.P., 2001. Hsp27: novel regulator of intracellular redox state. IUBMB Life 52, 303–307.

    PubMed  CAS  Google Scholar 

  • Arrigo, A.P., 2005a. Heat shock proteins as molecular chaperones. Med Sci (Paris). 21, 619–625.

    Google Scholar 

  • Arrigo, A.P., 2005b. In search of the molecular mechanism by which small stress proteins counteract apoptosis during cellular differentiation. J Cell Biochem 94, 241–246.

    Article  CAS  Google Scholar 

  • Arrigo, A.P., Firdaus, W.J., Mellier, G., Moulin, M., Paul, C., Diaz-Latoud, C., Kretz-Remy, C., 2005a. Cytotoxic effects induced by oxidative stress in cultured mammalian cells and protection provided by Hsp27 expression. Methods 35, 126–138.

    Article  CAS  Google Scholar 

  • Arrigo, A.P., Paul, C., Ducasse, C., Manero, F., Kretz-Remy, C., Virot, S., Javouhey, E., Mounier, N., Diaz-Latoud, C., 2002a. Small stress proteins: novel negative modulators of apoptosis induced independently of reactive oxygen species. Prog Mol Subcell Biol 28, 185–204.

    CAS  Google Scholar 

  • Arrigo, A.P., Paul, C., Ducasse, C., Sauvageot, O., Kretz-Remy, C., 2002b. Small stress proteins: modulation of intracellular redox state and protection against oxidative stress. Prog Mol Subcell Biol 28, 171–184.

    CAS  Google Scholar 

  • Arrigo, A.P., Virot, S., Chaufour, S., Firdaus, W., Kretz-Remy, C., Diaz-Latoud, C., 2005b. Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Signal 7, 414–422.

    Article  CAS  Google Scholar 

  • Atkins, D., Lichtenfels, R., Seliger, B., 2005. Heat shock proteins in renal cell carcinomas. Contrib Nephrol. 148, 35–56.

    PubMed  CAS  Google Scholar 

  • Baek, S.H., Min, J.N., Park, E.M., Han, M.Y., Lee, Y.S., Lee, Y.J., Park, Y.M., 2000. Role of small heat shock protein HSP25 in radioresistance and glutathione-redox cycle. J Cell Physiol 183, 100–107.

    Article  PubMed  CAS  Google Scholar 

  • Bausero, M.A., Bharti, A., Page, D.T., Perez, K.D., Eng, J.W., Ordonez, S.L., Asea, E.E., Jantschitsch, C., Kindas-Muegge, I., Ciocca, D., Asea, A., 2006. Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell. Tumour Biol. 27, 17–26.

    Article  PubMed  CAS  Google Scholar 

  • Berrieman, H.K., Cawkwell, L., O’KaneS, L., Smith, L., 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, 283–286.

    PubMed  Google Scholar 

  • Bielka, H., Hoinkis, G., Oesterreich, S., Stahl, J., Benndorf, R., 1994. Induction of the small stress protein, hsp25, in Ehrlich ascites carcinoma cells by anticancer drugs. FEBS Lett 343, 165–167.

    Article  PubMed  CAS  Google Scholar 

  • Bova, M.P., Yaron, O., Huang, Q., Ding, L., Haley, D.A., Stewart, P.L., Horwitz, J., 1999. Mutation R120G in alphaB-crystallin, which is linked to a desmin- related myopathy, results in an irregular structure and defective chaperone-like function. Proc Natl Acad Sci U S A 96, 6137–6142.

    Article  PubMed  CAS  Google Scholar 

  • Brar, B.K., Stephanou, A., Wagstaff, M.J., Coffin, R.S., Marber, M.S., Engelmann, G., Latchman, D.S., 1999. Heat shock proteins delivered with a virus vector can protect cardiac cells against apoptosis as well as against thermal or hypoxic stress. J Mol Cell Cardiol 31, 135–146.

    Article  PubMed  CAS  Google Scholar 

  • Bruey, J.M., Ducasse, C., Bonniaud, P., Ravagnan, L., Susin, S.A., Diaz-Latoud, C., Gurbuxani, S., Arrigo, A.P., Kroemer, G., Solary, E., Garrido, C., 2000a. Hsp27 negatively regulates cell death by interacting with cytochrome c. Nat Cell Biol 2, 645–652.

    Article  CAS  Google Scholar 

  • Bruey, J.M., Paul, C., Fromentin, A., Hilpert, S., Arrigo, A.P., Solary, E., Garrido, C., 2000b. Differential regulation of HSP27 oligomerization in tumor cells grown in vitro and in vivo. Oncogene 19, 4855–4863.

    Article  CAS  Google Scholar 

  • Calderwood, S.K., Khaleque, M.A., Sawyer, D.B., Ciocca, D.R., 2006. Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci. 31, 164–172.

    Article  PubMed  CAS  Google Scholar 

  • Carper, S.W., Rocheleau, T.A., Cimino, D., Storm, F.K., 1997. Heat shock protein 27 stimulates recovery of RNA and protein synthesis following a heat shock. J Cell Biochem 66, 153–164.

    Article  PubMed  CAS  Google Scholar 

  • Ceballos, E., Munoz-Alonso, M.J., Berwanger, B., Acosta, J.C., Hernandez, R., Krause, M., Hartmann, O., Eilers, M., Leon, J., 2005. Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes. Oncogene. 24, 4559–4571.

    CAS  Google Scholar 

  • Charette, S.J., Lavoie, J.N., Lambert, H., Landry, J., 2000. Inhibition of daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol 20, 7602–7612.

    Article  PubMed  CAS  Google Scholar 

  • 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., Anderson, K.C., 2003a. Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance. Blood 102, 3379–3386.

    Article  CAS  Google Scholar 

  • Chauhan, D., Li, G., Shringarpure, R., Podar, K., Ohtake, Y., Hideshima, T., Anderson, K.C., 2003b. Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells. Cancer Res 63, 6174–6177.

    CAS  Google Scholar 

  • Chelouche-Lev, D., Kluger, H.M., Berger, A.J., Rimm, D.L., Price, J.E., 2004. alphaB-crystallin as a marker of lymph node involvement in breast carcinoma. Cancer. 100, 2543–2548.

    Article  PubMed  CAS  Google Scholar 

  • Chen, H., Zheng, C., Zhang, Y., Chang, Y.Z., Qian, Z.M., Shen, X., 2006. Heat shock protein 27 downregulates the transferrin receptor 1-mediated iron uptake. Int J Biochem Cell Biol. 38, 1402–1416.

    Article  PubMed  CAS  Google Scholar 

  • Chen, J., Kahne, T., Rocken, C., Gotze, T., Yu, J., Sung, J.J., Chen, M., Hu, P., Malfertheiner, P., Ebert, M.P., 2004. Proteome analysis of gastric cancer metastasis by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry for identification of metastasis-related proteins. J Proteome Res. 3, 1009–1016.

    Article  PubMed  CAS  Google Scholar 

  • Ciocca, D.R., Calderwood, S.K., 2005. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 10, 86–103.

    Article  PubMed  CAS  Google Scholar 

  • Ciocca, D.R., Fuqua, S.A.W., Lock-Lim, S., Toft, D.O., Welch, W.J., McGuire, W.L., 1992. Response of human breast cancer cells to heat shock and chemotherapeutic drugs. Cancer Res. 52, 3648–3654.

    PubMed  CAS  Google Scholar 

  • Ciocca, D.R., Stati, A.O., Fanelli, M.A., Gaestel, M., 1996. Expression of heat shock protein 25,000 in rat uterus during pregnancy and pseudopregnancy. Biol Reprod 54, 1326–1335.

    Article  PubMed  CAS  Google Scholar 

  • Ciocca, D.R., trayssinet, P., Dario Cuello-Carrion. 2007. A pilot study with a therapeutic vaccine based on hydroxyapatite ceramic particles and delf-antijens in cancer patients. Cell Stress Chaperones 12, 33–43.

    Article  PubMed  CAS  Google Scholar 

  • Colas, P., Cohen, B., Jessen, T., Grishina, I., McCoy, J., Brent, R., 1996. Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature. 380, 548–550.

    Article  PubMed  CAS  Google Scholar 

  • Concannon, C.G., Gorman, A.M., Samali, A., 2003. On the role of Hsp27 in regulating apoptosis. Apoptosis 8, 61–70.

    Article  PubMed  CAS  Google Scholar 

  • Cornford, P.A., Dodson, A.R., Parsons, K.F., Desmond, A.D., Woolfenden, A., Fordham, M., Neoptolemos, J.P., Ke, Y., Foster, C.S., 2000. Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Res. 60, 7099–7105.

    PubMed  CAS  Google Scholar 

  • Cuesta, R., Laroia, G., Schneider, R.J., 2000. Chaperone Hsp27 inhibits translation during heat shock by binding eIF4G and facilitating dissociation of cap-initiation complexes. Genes Dev 14, 1460–1470.

    PubMed  CAS  Google Scholar 

  • de Jong, W., Leunissen, J., Voorter, C., 1993. Evolution of the alpha-crystallin/small heat-shock protein family. Mol Biol Evol 10, 103–126.

    PubMed  Google Scholar 

  • den Engelsman, J., Keijsers, V., de Jong, W.W., Boelens, W.C., 2003. The small heat-shock protein alpha B-crystallin promotes FBX4-dependent ubiquitination. J Biol Chem. 278, 4699–4704.

    Article  CAS  Google Scholar 

  • Diaz, N., Minton, S., Cox, C., Bowman, T., Gritsko, T., Garcia, R., Eweis, I., Wloch, M., Livingston, S., Seijo, E., Cantor, A., Lee, J.H., Beam, C.A., Sullivan, D., Jove, R., Muro-Cacho, C.A., 2006. Activation of stat3 in primary tumors from high-risk breast cancer patients is associated with elevated levels of activated SRC and survivin expression. Clin Cancer Res. 12, 20–28.

    Article  PubMed  CAS  Google Scholar 

  • Ehrnsperger, M., Gaestel, M., Buchner, J., 2000. Analysis of chaperone properties of small Hsp’s. Methods Mol Biol 99, 421–429.

    PubMed  CAS  Google Scholar 

  • Ehrnsperger, M., Graber, S., Gaestel, M., Buchner, J., 1997. Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation. EMBO J 16, 221–229.

    Article  PubMed  CAS  Google Scholar 

  • Fabre-Jonca, N., Gonin, S., Diaz-Latoud, C., Rouault, J.P., Arrigo, A.P., 1995. Thermal sensitivity in NIH 3T3 fibroblasts transformed by the v-fos oncogene. Correlation with reduced accumulation of 68-kDa and 25-kDa stress proteins after heat shock. Eur J Biochem 232, 118–128.

    Article  PubMed  CAS  Google Scholar 

  • Farokhzad, O.C., Cheng, J., Teply, B.A., Sherifi, I., Jon, S., Kantoff, P.W., Richie, J.P., Langer, R., 2006a. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci U S A. 103, 6315–6320.

    Article  CAS  Google Scholar 

  • Farokhzad, O.C., Karp, J.M., Langer, R., 2006b. Nanoparticle-aptamer bioconjugates for cancer targeting. Expert Opin Drug Deliv. 3, 311–324.

    Article  CAS  Google Scholar 

  • 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., Tang, Z.Y., 2005. Heat-shock protein 27: a potential biomarker for hepatocellular carcinoma identified by serum proteome analysis. Proteomics. 5, 4581–4588.

    Article  PubMed  CAS  Google Scholar 

  • Firdaus, W.J., Wyttenbach, A., Diaz-Latoud, C., Currie, R.W., Arrigo, A.P., 2006. Analysis of oxidative events induced by expanded polyglutamine huntingtin exon 1 that are differentially restored by expression of heat shock proteins or treatment with an antioxidant. Febs J. 273, 3076–3093.

    Article  PubMed  CAS  Google Scholar 

  • Gao, C., Zou, Z., Xu, L., Moul, J., Seth, P., Srivastava, S., 2000. p53-dependent induction of heat shock protein 27 (HSP27) expression. Int J Cancer 88, 191–194.

    Article  PubMed  CAS  Google Scholar 

  • Garrido, C., 2002. Size matters: of the small HSP27 and its large oligomers. Cell Death Differ 9, 483–485.

    Article  PubMed  CAS  Google Scholar 

  • Garrido, C., Bruey, J.M., Fromentin, A., Hammann, A., Arrigo, A.P., Solary, E., 1999. HSP27 inhibits cytochrome c-dependent activation of procaspase-9. Faseb J 13, 2061–2070.

    PubMed  CAS  Google Scholar 

  • Garrido, C., Brunet, M., Didelot, C., Zermati, Y., Schmitt, E., Kroemer, G., 2006. Heat Shock Proteins 27 and 70: Anti-Apoptotic Proteins with Tumorigenic Properties. Cell Cycle 5, 22.

    Google Scholar 

  • Garrido, C., Fromentin, A., Bonnotte, B., Favre, N., Moutet, M., Arrigo, A.P., Mehlen, P., Solary, E., 1998. Heat shock protein 27 enhances the tumorigenicity of immunogenic rat colon carcinoma cell clones. Cancer Res 58, 5495–5499.

    PubMed  CAS  Google Scholar 

  • Garrido, C., Gurbuxani, S., Ravagnan, L., Kroemer, G., 2001. Heat shock proteins: endogenous modulators of apoptotic cell death. Biochem Biophys Res Commun 286, 433–442.

    Article  PubMed  CAS  Google Scholar 

  • Garrido, C., Mehlen, P., Fromentin, A., Hammann, A., Assem, M., Arrigo, A.-P., 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, 653–659.

    Article  PubMed  CAS  Google Scholar 

  • Garrido, C., Ottavi, P., Fromentin, A., Hammann, A., Arrigo, A.P., Chauffert, B., Mehlen, P., 1997. HSP27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs. Cancer Res 57, 2661–2667.

    PubMed  CAS  Google Scholar 

  • Georgakis, G.V., Younes, A., 2005. Heat-shock protein 90 inhibitors in cancer therapy: 17AAG and beyond. Future Oncol. 1, 273–281.

    Article  PubMed  CAS  Google Scholar 

  • Gonin, S., Fabre-Jonca, N., Diaz-Latoud, C., Rouault, J.P., Arrigo, A.P., 1997. Transformation by T-antigen and other oncogenes delays Hsp25 accumulation in heat shocked NIH 3T3 fibroblasts. Cell Stress Chaperones 2, 238–251.

    Article  PubMed  CAS  Google Scholar 

  • Gritsko, T., Williams, A., Turkson, J., Kaneko, S., Bowman, T., Huang, M., Nam, S., Eweis, I., Diaz, N., Sullivan, D., Yoder, S., Enkemann, S., Eschrich, S., Lee, J.H., Beam, C.A., Cheng, J., Minton, S., Muro-Cacho, C.A., Jove, R., 2006. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res. 12, 11–19.

    Article  PubMed  CAS  Google Scholar 

  • Gruvberger-Saal, S.K., Parsons, R., 2006. Is the small heat shock protein alphaB-crystallin an oncogene? J Clin Invest. 116, 30–32.

    Article  PubMed  CAS  Google Scholar 

  • Hahn, G.M., Li, G.C., 1982a. Interactions of hyperthermia and drugs: treatments and probes. Natl Cancer Inst Monogr 61, 317–323.

    CAS  Google Scholar 

  • Hahn, G.M., Li, G.C., 1982b. Thermotolerance and heat shock proteins in mammalian cells. Radiat Res 92, 452–457.

    Article  CAS  Google Scholar 

  • Hollander, J.M., Martin, J.L., Belke, D.D., Scott, B.T., Swanson, E., Krishnamoorthy, V., Dillmann, W.H., 2004. Overexpression of wild-type heat shock protein 27 and a nonphosphorylatable heat shock protein 27 mutant protects against ischemia/reperfusion injury in a transgenic mouse model. Circulation 110, 3544–3552. Epub 2004 Nov 3529.

    Article  PubMed  CAS  Google Scholar 

  • Huot, J., Houle, F., Marceau, F., Landry, J., 1997. Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. Circ Res 80, 383–392.

    PubMed  CAS  Google Scholar 

  • Huot, J., Houle, F., Spitz, D.R., Landry, J., 1996. HSP27 phosphorylation-mediated resistance against actin fragmentation and cell death induced by oxidative stress. Cancer Res. 56, 273–279.

    PubMed  CAS  Google Scholar 

  • Huot, J., Roy, G., Lambert, H., Chretien, P., Landry, J., 1991. Increased survival after treatments with anticancer agents of Chinese hamster cells expressing the human Mr 27,000 heat shock protein. Cancer Res. 51, 5245–5252.

    PubMed  CAS  Google Scholar 

  • Ingolia, T.D., Craig, E.A., 1982. Four small heat shock proteins are related to each other and to mammalian a-crystallin. Proc. Natl. Acad. Sci. USA 79, 2360–2364.

    Article  PubMed  CAS  Google Scholar 

  • Jäättela, M., 1999. Escaping cell death: survival proteins in cancer. Exp Cell Res 248, 30–43.

    Article  PubMed  Google Scholar 

  • Jäättelä, M., 1993. Overexpression of major heat shock protein hsp70 inhibits tumor necrosis factor-induced activation of phospholipase A2. J. Immunol. 151, 4286–4294.

    PubMed  Google Scholar 

  • Jacobson, M.D., 1996. Reactive oxygen species and programmed cell death. Trends Biochem. Sci. 21, 83–86.

    Article  PubMed  CAS  Google Scholar 

  • Kamradt, M.C., Chen, F., Cryns, V.L., 2001. The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. J Biol Chem. 276, 16059–16063.

    Article  PubMed  CAS  Google Scholar 

  • Kamradt, M.C., Chen, F., Sam, S., Cryns, V.L., 2002. The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation. J Biol Chem 277, 38731–38736.

    Article  PubMed  CAS  Google Scholar 

  • Kamradt, M.C., Lu, M., Werner, M.E., Kwan, T., Chen, F., Strohecker, A., Oshita, S., Wilkinson, J.C., Yu, C., Oliver, P.G., Duckett, C.S., Buchsbaum, D.J., LoBuglio, A.F., Jordan, V.C., Cryns, V.L., 2005. The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem. 280, 11059–11066.

    Article  PubMed  CAS  Google Scholar 

  • Kato, K., Hasegawa, K., Goto, S., Inaguma, Y., 1994. Dissociation as a result of phosphorylation of an aggregated form of the small stress protein, hsp27. J. Biol. Chem. 269, 11274–11278.

    PubMed  CAS  Google Scholar 

  • Kato, K., Ito, H., Kamei, K., Inaguma, Y., Iwamoto, I., Saga, S., 1998. Phosphorylation of alphaB-crystallin in mitotic cells and identification of enzymatic activities responsible for phosphorylation. J Biol Chem. 273, 28346–28354.

    Article  PubMed  CAS  Google Scholar 

  • Kimbro, K.S., Simons, J.W., 2006. Hypoxia-inducible factor-1 in human breast and prostate cancer. Endocr Relat Cancer. 13, 739–749.

    Article  PubMed  CAS  Google Scholar 

  • Korneeva, I., Caputo, T.A., Witkin, S.S., 2002. Cell-free 27 kDa heat shock protein (hsp27) and hsp27-cytochrome c complexes in the cervix of women with ovarian or endometrial cancer. Int J Cancer. 102, 483–486.

    Article  PubMed  CAS  Google Scholar 

  • Latchman, D.S., 2005. HSP27 and cell survival in neurones. Int J Hyperthermia. 21, 393–402.

    Article  PubMed  CAS  Google Scholar 

  • Lavoie, J.N., Lambert, H., Hickey, E., Weber, L.A., Landry, J., 1995. Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol. Cell. Biol. 15, 505–516.

    PubMed  CAS  Google Scholar 

  • Lee, G.J., Roseman, A.M., Saibil, H.R., Vierling, E., 1997. A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state. EMBO J 16, 659–671.

    Article  PubMed  CAS  Google Scholar 

  • Lelj-Garolla, B., Mauk, A.G., 2005. Self-association of a small heat shock protein. J Mol Biol 345, 631–642.

    Article  PubMed  CAS  Google Scholar 

  • Levine, R.L., Garland, D., Oliver, C.N., Amici, A., Climent, I., Lenz, A.G., Ahn, B.W., Shaltiel, S., Stadtman, E.R., 1990. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186, 464–478.

    Article  PubMed  CAS  Google Scholar 

  • Libermann, T.A., Zerbini, L.F., 2006. Targeting transcription factors for cancer gene therapy. Curr Gene Ther. 6, 17–33.

    Article  PubMed  CAS  Google Scholar 

  • Ludwig, H., Khayat, D., Giaccone, G., Facon, T., 2005. Proteasome inhibition and its clinical prospects in the treatment of hematologic and solid malignancies. Cancer 104, 1794–1807.

    Article  PubMed  CAS  Google Scholar 

  • Luk, J.M., Lam, C.T., Siu, A.F., Lam, B.Y., Ng, I.O., Hu, M.Y., Che, C.M., Fan, S.T., 2006. Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values. Proteomics. 6, 1049–1057.

    Article  PubMed  CAS  Google Scholar 

  • Mao, Y.W., Liu, J.P., Xiang, H., Li, D.W., 2004. Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. Cell Death Differ. 11, 512–526.

    Article  PubMed  CAS  Google Scholar 

  • Marin-Vinader, L., Shin, C., Onnekink, C., Manley, J.L., Lubsen, N.H., 2005. Hsp27 Enhances Recovery of Splicing as well as Rephosphorylation of SRp38 after Heat Shock. Mol Biol Cell 7, 7.

    Google Scholar 

  • McCollum, A.K., Teneyck, C.J., Sauer, B.M., Toft, D.O., Erlichman, C., 2006. Up-regulation of Heat Shock Protein 27 Induces Resistance to 17-Allylamino-Demethoxygeldanamycin through a Glutathione-Mediated Mechanism. Cancer Res. 66, 10967–10975.

    Article  PubMed  CAS  Google Scholar 

  • Mehlen, P., Briolay, J., Smith, L., Diaz-Latoud, C., Pauli, D., Arrigo, A.-P., 1993. Analysis of the resistance to heat and hydrogen peroxide stresses in COS cells transiently expressing wid type or deletion mutants of the Drosophila 27-kDa heat-shock protein. Eur J Biochem 215, 277–284.

    Article  PubMed  CAS  Google Scholar 

  • Mehlen, P., Coronas, V., Ljubic-Thibal, V., Ducasse, C., Granger, L., Jourdan, F., Arrigo, A.P., 1999. Small stress protein Hsp27 accumulation during dopamine-mediated differentiation of rat olfactory neurons counteracts apoptosis. Cell Death Differ 6, 227–233.

    Article  PubMed  CAS  Google Scholar 

  • Mehlen, P., Hickey, E., Weber, L., Arrigo, A.-P., 1997a. Large unphosphorylated aggregates as the active form of hsp27 which controls intracellular reactive oxygen species and glutathione levels and generates a protection against TNFα in NIH-3T3-ras cells. Biochem Biophys Res Comm 241, 187–192.

    Article  CAS  Google Scholar 

  • Mehlen, P., Mehlen, A., Godet, J., Arrigo, A.-P., 1997b. hsp27 as a Switch between Differentiation and Apoptosis in Murine Embryonic Stem Cells. J. Biol Chem 272, 31657–31665.

    Article  CAS  Google Scholar 

  • Mehlen, P., Mehlen, A., Guillet, D., Préville, X., Arrigo, A.-P., 1995a. Tumor necrosis factor-a induces changes in the phosphorylation, cellular localization, and oligomerization of human hsp27, a stress protein that confers cellular resistance to this cytokine. J Cell Biochem 58, 248–259.

    Article  CAS  Google Scholar 

  • Mehlen, P., Préville, X., Chareyron, P., Briolay, J., Klemenz, R., Arrigo, A.-P., 1995b. Constitutive expression of human hsp27, Drosophila hsp27, or human alpha B-crystallin confers resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J Immunol 154, 363–374.

    CAS  Google Scholar 

  • Mehlen, P., Préville, X., Kretz-Remy, C., Arrigo, A.-P., 1996a. Human hsp27, Drosophila hsp27 and human αB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these protein against TNFα-induced cell death. EMBO J 15, 2695–2706.

    CAS  Google Scholar 

  • Mehlen, P., Schulze-Osthoff, K., Arrigo, A.P., 1996b. Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death. The Journal of Biological Chemistry 271, 16510–16514.

    Article  CAS  Google Scholar 

  • Morrow, G., Samson, M., Michaud, S., Tanguay, R.M., 2004. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. Faseb J 18, 598–599.

    PubMed  CAS  Google Scholar 

  • Moulin, M., Arrigo, A.P., 2006. Long lasting heat shock stimulation of TRAIL-induced apoptosis in transformed T lymphocytes. Exp Cell Res. 312, 1765–1784.

    Article  PubMed  CAS  Google Scholar 

  • Moulin, M., Dumontet, C., Arrigo, A.P., 2007. Sensitization of Chronic Lymphocytic Leukemia cells to TRAIL-induced apoptosis by hyperthermia. Cancer Letters. 250, 117–127.

    Article  PubMed  CAS  Google Scholar 

  • Mounier, N., Arrigo, A.P., 2002. Actin cytoskeleton and small heat shock proteins: how do they interact? Cell Stress Chaperones 7, 167–176.

    Article  PubMed  CAS  Google Scholar 

  • Moyano, J.V., Evans, J.R., Chen, F., Lu, M., Werner, M.E., Yehiely, F., Diaz, L.K., Turbin, D., Karaca, G., Wiley, E., Nielsen, T.O., Perou, C.M., Cryns, V.L., 2006. AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. J Clin Invest. 116, 261–270.

    Google Scholar 

  • Nefti, O., Grongnet, J.F., David, J.C., 2005. Overexpression of alphaB crystallin in the gastrointestinal tract of the newborn piglet after hypoxia. Shock. 24, 455–461.

    Article  PubMed  CAS  Google Scholar 

  • Oesterreich, S., Hilsenbeck, S.G., Ciocca, D.R., Allred, D.C., Clark, G.M., Chamness, G.C., Osborne, C.K., Fuqua, S.A., 1996. The small heat shock protein HSP27 is not an independent prognostic marker in axillary lymph node-negative breast cancer patients. Clin Cancer Res 2, 1199–1206.

    PubMed  CAS  Google Scholar 

  • Oesterreich, S., Schunck, H., Benndorf, R., Bielka, H., 1991. Cisplatin induces the small heat shock protein hsp25 and thermotolerance in Ehrlich ascites tumor cells. Biochem Biophys Res Commun 180, 243–248.

    Article  PubMed  CAS  Google Scholar 

  • Oesterreich, S., Weng, C.-N., Qiu, M., Hilsenbeck, S.G., Osborne, C.K., Fuqua, S.W., 1993. The small heat shock protein hsp27 is correlated with growth and drug resistance in human breast cancer cell lines. Cancer Res. 53, 4443–4448.

    PubMed  CAS  Google Scholar 

  • Pandey, P., Farber, R., Nakazawa, A., Kumar, S., Bharti, A., Nalin, C., Weichselbaum, R., Kufe, D., Kharbanda, S., 2000. Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3. Oncogene 19, 1975–1981.

    Article  PubMed  CAS  Google Scholar 

  • Parcellier, A., Gurbuxani, S., Schmitt, E., Solary, E., Garrido, C., 2003a. Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. Biochem Biophys Res Commun 304, 505–512.

    Article  CAS  Google Scholar 

  • Parcellier, A., Schmitt, E., Brunet, M., Hammann, A., Solary, E., Garrido, C., 2005. Small heat shock proteins HSP27 and alphaB-crystallin: cytoprotective and oncogenic functions. Antioxid Redox Signal. 7, 404–413.

    Article  PubMed  CAS  Google Scholar 

  • Parcellier, A., Schmitt, E., Gurbuxani, S., Seigneurin-Berny, D., Pance, A., Chantome, A., Plenchette, S., Khochbin, S., Solary, E., Garrido, C., 2003b. HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation. Mol Cell Biol 23, 5790–5802.

    Article  CAS  Google Scholar 

  • Park, Y.M., Han, M.Y., Blackburn, R.V., Lee, Y.J., 1998. Overexpression of HSP25 reduces the level of TNF alpha-induced oxidative DNA damage biomarker, 8-hydroxy-2’-deoxyguanosine, in L929 cells. J Cell Physiol 174, 27–34.

    Article  PubMed  CAS  Google Scholar 

  • Paul, C., Arrigo, A.P., 2000. Comparison of the protective activities generated by two survival proteins: Bcl-2 and Hsp27 in L929 murine fibroblasts exposed to menadione or staurosporine. Exp Gerontol 35, 757–766.

    Article  PubMed  CAS  Google Scholar 

  • Paul, C., Manero, F., Gonin, S., Kretz-Remy, C., Virot, S., Arrigo, A.P., 2002. Hsp27 as a negative regulator of cytochrome C release. Mol Cell Biol 22, 816–834.

    Article  PubMed  CAS  Google Scholar 

  • Perou, C.M., Sorlie, T., Eisen, M.B., van de Rijn, M., Jeffrey, S.S., Rees, C.A., Pollack, J.R., Ross, D.T., Johnsen, H., Akslen, L.A., Fluge, O., Pergamenschikov, A., Williams, C., Zhu, S.X., Lonning, P.E., Borresen-Dale, A.L., Brown, P.O., Botstein, D., 2000. Molecular portraits of human breast tumours. Nature. 406, 747–752.

    Article  PubMed  CAS  Google Scholar 

  • Préville, X., Gaestel, M., Arrigo, A.P., 1998a. Phosphorylation is not essential for protection of L929 cells by Hsp25 against H_2O_2-mediated disruption actin cytoskeleton, a protection which appears related to the redox change mediated by Hsp25. Cell Stress Chaperones 3, 177–187.

    Article  Google Scholar 

  • Preville, X., Salvemini, F., Giraud, S., Chaufour, S., Paul, C., Stepien, G., Ursini, M.V., Arrigo, A. P., 1999. Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery. Exp Cell Res 247, 61–78.

    Article  PubMed  CAS  Google Scholar 

  • Préville, X., Schultz, H., Knauf, U., Gaestel, M., Arrigo, A.P., 1998b. Analysis of the role of Hsp25 phosphorylation reveals the importance of the oligomerization state of this small heat shock protein in its protective function against TNFalpha- and hydrogen peroxide-induced cell death. J Cell Biochem 69, 436–452.

    Article  Google Scholar 

  • Rane, M.J., Pan, Y., Singh, S., Powell, D.W., Wu, R., Cummins, T., Chen, Q., McLeish, K.R., Klein, J.B., 2003. Heat shock protein 27 controls apoptosis by regulating akt activation. J Biol Chem 278, 27828–27835.

    Article  PubMed  CAS  Google Scholar 

  • Rocchi, P., Beraldi, E., Ettinger, S., Fazli, L., Vessella, R.L., Nelson, C., 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, 11083–11093.

    Article  PubMed  CAS  Google Scholar 

  • Rocchi, P., Jugpal, P., So, A., Sinneman, S., Ettinger, S., Fazli, L., Nelson, C., 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 98, 1028–1089.

    Article  CAS  Google Scholar 

  • Rocchi, P., So, A., Kojima, S., Signaevsky, M., Beraldi, E., Fazli, L., Hurtado-Coll, A., Yamanaka, K., Gleave, M., 2004. Heat shock protein 27 increases after androgen ablation and plays a cytoprotective role in hormone-refractory prostate cancer. Cancer Res. 64, 6595–6602.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Rouse, J., Cohen, P., Trigon, S., Morange, M., Alonso-Llamazares, A., Zamanillo, D., Hunt, T., Nebreda, A. R., 1994. A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78, 1027–1037.

    Article  PubMed  CAS  Google Scholar 

  • Rugo, R.E., Secretan, M.B., Schiestl, R.H., 2002. X radiation causes a persistent induction of reactive oxygen species and a delayed reinduction of TP53 in normal human diploid fibroblasts. Radiat Res. 158, 210–219.

    Article  PubMed  CAS  Google Scholar 

  • Samali, A., Cotter, T.G., 1996. Heat shock proteins increase resistance to apoptosis. Exp Cell Res 223, 163–170.

    Article  PubMed  CAS  Google Scholar 

  • Samali, A., Nordgren, H., Zhivotovsky, B., Peterson, E., Orrenius, S., 1999. A comparative study of apoptosis and necrosis in HepG2 cells: oxidant- induced caspase inactivation leads to necrosis. Biochem Biophys Res Commun 255, 6–11.

    Article  PubMed  CAS  Google Scholar 

  • Schmitt, E., Gehrmann, M., Brunet, M., Multhoff, G., Garrido, C., 2006. Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol 81, 15–27.

    Article  PubMed  CAS  Google Scholar 

  • Shin, K.D., Lee, M.Y., Shin, D.S., Lee, S., Son, K.H., Koh, S., Paik, Y.K., Kwon, B.M., Han, D.C., 2005. Blocking tumor cell migration and invasion with biphenyl isoxazole derivative KRIBB3, a synthetic molecule that inhibits Hsp27 phosphorylation. J Biol Chem. 280, 41439–41448.

    Article  PubMed  CAS  Google Scholar 

  • Sitte, N., Merker, K., Grune, T., 1998. Proteasome-dependent degradation of oxidized proteins in MRC-5 fibroblasts. FEBS Lett 440, 399-402.

    Article  PubMed  CAS  Google Scholar 

  • Song, H., Ethier, S.P., Dziubinski, M.L., Lin, J., 2004. Stat3 modulates heat shock 27kDa protein expression in breast epithelial cells. Biochem Biophys Res Commun. 314, 143–150.

    Article  PubMed  CAS  Google Scholar 

  • Song, H.Y., Liu, Y.K., Feng, J.T., Cui, J.F., Dai, Z., Zhang, L.J., Feng, J.X., Shen, H.L., Tang, Z.Y., 2006. Proteomic analysis on metastasis-associated proteins of human hepatocellular carcinoma tissues. J Cancer Res Clin Oncol. 132, 92–98.

    Article  PubMed  CAS  Google Scholar 

  • Sorlie, T., Perou, C.M., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M.B., van de Rijn, M., Jeffrey, S.S., Thorsen, T., Quist, H., Matese, J.C., Brown, P.O., Botstein, D., Eystein Lonning, P., Borresen-Dale, A.L., 2001. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 98, 10869–10874.

    Article  PubMed  CAS  Google Scholar 

  • Strahler, J.R., Kuick, R., Hanash, S.M., 1991. Diminished phosphorylation of a heat shock protein (HSP 27) in infant acute lymphoblastic leukemia. Biochem Biophys Res Commun. 175, 134–142.

    Article  PubMed  CAS  Google Scholar 

  • Takashi, M., Katsuno, S., Sakata, T., Ohshima, S., Kato, K., 1998. Different concentrations of two small stress proteins, alphaB crystallin and HSP27 in human urological tumor tissues. Urol Res. 26, 395–399.

    Article  PubMed  CAS  Google Scholar 

  • Takashi, M., Sakata, T., Ohmura, M., Kato, K., 1997. Elevated concentrations of the small stress protein HSP27 in rat renal tumors. Urol Res 25, 173–177.

    Article  PubMed  CAS  Google Scholar 

  • van Heijst, J.W., Niessen, H.W., Musters, R.J., van Hinsbergh, V.W., Hoekman, K., 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, 309–319.

    Article  PubMed  CAS  Google Scholar 

  • Verrills, N.M., Liem, N.L., Liaw, T.Y., Hood, B.D., Lock, R.B., Kavallaris, M., 2006. Proteomic analysis reveals a novel role for the actin cytoskeleton in vincristine resistant childhood leukemia–an in vivo study. Proteomics. 6, 1681–1694.

    Article  PubMed  CAS  Google Scholar 

  • Vicart, P., Caron, A., Guicheney, P., Li, Z., Prevost, M.C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J.M., Paulin, D., Fardeau, M., 1998. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20, 92–95.

    Article  PubMed  CAS  Google Scholar 

  • Wang, G., Klostergaard, J., Khodadadian, M., Wu, J., Wu, T.W., Fung, K.P., Carper, S.W., Tomasovic, S.P., 1996. Murine cells transfected with human Hsp27 cDNA resist TNF-induced cytotoxicity. J Immunother Emphasis Tumor Immunol 19, 9–20.

    PubMed  CAS  Google Scholar 

  • Webster, K.A., 2003. Serine phosphorylation and suppression of apoptosis by the small heat shock protein alphaB-crystallin. Circ Res. 92, 130–132.

    Article  PubMed  CAS  Google Scholar 

  • Whitlock, N.A., Agarwal, N., Ma, J.X., Crosson, C.E., 2005. Hsp27 upregulation by HIF-1 signaling offers protection against retinal ischemia in rats. Invest Ophthalmol Vis Sci. 46, 1092–1098.

    Article  PubMed  Google Scholar 

  • Wulfkuhle, J.D., Sgroi, D.C., Krutzsch, H., McLean, K., McGarvey, K., Knowlton, M., Chen, S., Shu, H., Sahin, A., Kurek, R., Wallwiener, D., Merino, M.J., Petricoin, E.F., 3rd, Zhao, Y., Steeg, P.S., 2002. Proteomics of human breast ductal carcinoma in situ. Cancer Res. 62, 6740–6749.

    PubMed  CAS  Google Scholar 

  • Xiao, K., Liu, W., Qu, S., Sun, H., Tang, J., 1996. Study of heat shock protein HSP90 alpha, HSP70, HSP27 mRNA expression in human acute leukemia cells. J Tongji Med Univ. 16, 212–216.

    Article  PubMed  CAS  Google Scholar 

  • Xu, L., Chen, S., 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, 2987–2998.

    Article  PubMed  CAS  Google Scholar 

  • Yan, L.J., Christians, E.S., Liu, L., Xiao, X., Sohal, R.S., Benjamin, I.J., 2002. Mouse heat shock transcription factor 1 deficiency alters cardiac redox homeostasis and increases mitochondrial oxidative damage. Embo J 21, 5164–5172.

    Article  PubMed  CAS  Google Scholar 

  • Zucker, B., Hanusch, J., Bauer, G., 1997. Glutathione depletion in fibroblasts is the basis for apoptosis-induction by endogenous reactive oxygen species. Cell Death & Diff. 4, 388–395.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stress, Chaperons and Cell Death Laboratory CNRS UMR 5534, Centre de Génétique Moléculaire et Cellulaire, Université Claude Bernard, LYON 1, 16 rue Dubois, 69622 Villeurbanne Cedex, France

    Andre-Patrick Arrigo

Authors
  1. Andre-Patrick Arrigo
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Harvard Medical School, Boston, U.S.A

    Stuart K. Calderwood

  2. Boston University School of Medicine, Boston, U.S.A

    Michael Y. Sherman

  3. National Research Council CONICET, Mendoza, Argentina

    Daniel R. Ciocca

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer

About this chapter

Cite this chapter

Arrigo, AP. (2007). Anti-apoptotic, Tumorigenic and Metastatic Potential of Hsp27 (HspB1) and αB-crystallin (HspB5): Emerging Targets for the Development of New Anti-Cancer Therapeutic Strategies. In: Calderwood, S.K., Sherman, M.Y., Ciocca, D.R. (eds) Heat Shock Proteins in Cancer. Heat Shock Proteins, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6401-2_4

Download citation

Publish with us

Policies and ethics

Search

Navigation