Hsp70 in cancer: Back to the future

Oncogene

Volumn 34, Issue 32, 2015, Pages 4153-4161

  Sherman, M Y ^a   Gabai, V L ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BAG3 PROTEIN; HEAT SHOCK PROTEIN 70; PROTEIN; UNCLASSIFIED DRUG; APOPTOSIS REGULATORY PROTEIN; BAG3 PROTEIN, HUMAN; PROTEIN BINDING; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

CANCER CHEMOTHERAPY; GENE OVEREXPRESSION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; TUMOR CELL; ANIMAL; BIOLOGICAL MODEL; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NEOPLASM;

ANIMALIA;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; APOPTOSIS REGULATORY PROTEINS; GENE EXPRESSION REGULATION, NEOPLASTIC; HSP70 HEAT-SHOCK PROTEINS; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; PROTEIN BINDING; SIGNAL TRANSDUCTION;

EID: 84938974589     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2014.349     Document Type: Review

References (138)

1. Bukau B, Weissman J, Horwich A. Molecular chaperones and protein quality control. Cell 2006; 125: 443-451.
2. Buchberger A, Bukau B, Sommer T. protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms. Mol Cell 2010; 40: 238-252.
3. Morimoto RI. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 1998; 12: 3788-3796.
4. Voellmy R. Sensing stress and responding to stress. In: Feige U, Morimoto I, Yahara I, Polla B (eds). Stress-Inducible Cellular Responses vol. 77. Birkhauser Verlag: Basel, Switzerland, 1996, pp 121-137.
5. Jinwal UK, Akoury E, Abisambra JF, O'Leary JC 3rd, Thompson AD, Blair LJ et al. Imbalance of Hsp70 family variants fosters tau accumulation. FASEB J 2013; 27: 1450-1459.
6. Ciocca DR, Clark GM, Tandon AK, Fuqua SA, Welch WJ, McGuire WL. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst 1993; 85: 570-574.
7. Hwang TS, Han HS, Choi HK, Lee YJ, Kim YJ, Han MY et al. Differential, stage-dependent expression of Hsp70, Hsp110 and Bcl-2 in colorectal cancer. J Gastroenterol Hepatol 2003; 18: 690-700.
8. Joo M, Chi JG, Lee H. Expressions of HSP70 and HSP27 in hepatocellular carcinoma. J Korean Med Sci 2005; 20: 829-834.
9. Luk JM, Lam CT, Siu AF, Lam BY, Ng IO, Hu MY et al. Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat-shock proteins (Hsp27, Hsp70, GRP78) up-regulation and their associated prognostic values. Proteomics 2006; 6: 1049-1057.
10. Alaiya AA, Oppermann M, Langridge J, Roblick U, Egevad L, Brindstedt S et al. Identification of proteins in human prostate tumor material by two-dimensional gel electrophoresis and mass spectrometry. Cell Mol Life Sci 2001; 58: 307-311.
11. Tang D, Khaleque MA, Jones EL, Theriault JR, Li C, Wong WH et al. Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones 2005; 10: 46-58.
12. Wang XP, Wang QX, Li HY, Chen RF. Heat shock protein 70 chaperoned alpha-fetoprotein in human hepatocellular carcinoma cell line BEL-7402. World J Gastroenterol 2005; 11: 5561-5564.
13. Hellman K, Alaiya AA, Schedvins K, Steinberg W, Hellstrom AC, Auer G. Protein expression patterns in primary carcinoma of the vagina. Br J Cancer 2004; 91: 319-326.
14. Park CS, Joo IS, Song SY, Kim DS, Bae DS, Lee JH. An immunohistochemical analysis of heat shock protein 70, p53, and estrogen receptor status in carcinoma of the uterine cervix. Gynecol Oncol 1999; 74: 53-60.
15. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 2005; 10: 86-103.
16. Bauer K, Nitsche U, Slotta-Huspenina J, Drecoll E, von Weyhern CH, Rosenberg R et al. High HSP27 and HSP70 expression levels are independent adverse prognostic factors in primary resected colon cancer. Cell Oncol (Dordr) 2012; 35: 197-205.
17. Yu H-J, Chang Y-H, Pan C-C. Prognostic significance of heat shock proteins in urothelial carcinoma of the urinary bladder. Histopathology 2013; 62: 788-798.
18. Syrigos KN, Harrington KJ, Karayiannakis AJ, Sekara E, Chatziyianni E, Syrigou EI et al. Clinical significance of heat shock protein-70 expression in bladder cancer. Urology 2003; 61: 677-680.
19. Lee HW, Lee EH, Kim SH, Roh MS, Jung SB, Choi YC. Heat shock protein 70 (HSP70) expression is associated with poor prognosis in intestinal type gastric cancer. Virchows Arch 2013; 463: 489-495.
20. Shin E, Ryu HS, Kim SH, Jung H, Jang JJ, Lee K. The clinicopathological significance of heat shock protein 70 and glutamine synthetase expression in hepatocellular carcinoma. J Hepatobiliary Pancreat Sci 2011; 18: 544-550.
21. Ramp U, Mahotka C, Heikaus S, Shibata T, Grimm MO, Willers R et al. Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis. Histol Histopathol 2007; 22: 1099-1107.
22. Nakajima M, Kuwano H, Miyazaki T, Masuda N, Kato H. Significant correlation between expression of heat shock proteins 27, 70 and lymphocyte infiltration in esophageal squamous cell carcinoma. Cancer Lett 2002; 178: 99-106.
23. Boonjaraspinyo S, Boonmars T, Kaewkes S, Laummaunwai P, Pinlaor S, Loilome W et al. Down-regulated expression of HSP70 in correlation with clinicopathology of cholangiocarcinoma. Pathol Oncol Res 2012; 18: 227-237.
24. Tavassol F, Starke OF, Kokemuller H, Wegener G, Muller-Tavassol CC, Gellrich NC et al. Prognostic significance of heat shock protein 70 (HSP70) in patients with oral cancer. Head Neck Oncol 2011; 3: 10.
25. Malusecka E, Krzyzowska-Gruca S, Gawrychowski J, Fiszer-Kierzkowska A, Kolosza Z, Krawczyk Z. Stress proteins HSP27 and HSP70i predict survival in non-small cell lung carcinoma. Anticancer Res 2008; 28: 501-506.
26. Ricaniadis N, Kataki A, Agnantis N, Androulakis G, Karakousis CP. Long-term prognostic significance of HSP-70, c-myc and HLA-DR expression in patients with malignant melanoma. Eur J Surg Oncol 2001; 27: 88-93.
27. Tang D, Kang R, Xiao W, Wang H, Calderwood SK, Xiao X. The anti-inflammatory effects of heat shock protein 72 involve inhibition of high-mobility-group box 1 release and proinflammatory function in macrophages. J Immunol 2007; 179: 1236-1244.
28. Zheng Z, Kim JY, Ma H, Lee JE, Yenari MA. Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke. J Cereb Blood Flow Metab 2008; 28: 53-63.
29. Tanaka K, Namba T, Arai Y, Fujimoto M, Adachi H, Sobue G et al. Genetic evidence for a protective role for heat shock factor 1 and heat shock protein 70 against colitis. J Biol Chem 2007; 282: 23240-23252.
30. Chen H, Wu Y, Zhang Y, Jin L, Luo L, Xue B et al. Hsp70 inhibits lipopolysaccharide-induced NF-kappaB activation by interacting with TRAF6 and inhibiting its ubiquitination. FEBS Lett 2006; 580: 3145-3152.
31. Tao Y, Hart J, Lichtenstein L, Joseph LJ, Ciancio MJ, Hu S et al. Inducible heat shock protein 70 prevents multifocal flat dysplastic lesions and invasive tumors in an inflammatory model of colon cancer. Carcinogenesis 2009; 30: 175-182.
32. Calderwood SK, Theriault JR, Gong J. Message in a bottle: role of the 70-kDa heat shock protein family in anti-tumor immunity. Eur J Immunol 2005; 35: 2518-2527.
33. Bolhassani A, Rafati S. Heat-shock proteins as powerful weapons in vaccine development. Expert Rev Vaccines 2008; 7: 1185-1199.
34. Calderwood SK, Ciocca DR. Heat shock proteins: Stress proteins with Janus-like properties in cancer. Int J Hyperthermia 2008; 24: 31-39.
35. Cai MB, Wang XP, Zhang JX, Han HQ, Liu CC, Bei JX et al. Expression of heat shock protein 70 in nasopharyngeal carcinomas: different expression patterns correlate with distinct clinical prognosis. J Transl Med 2012; 10: 96.
36. Gabai VL, Zamulaeva IV, Mosin AF, Makarova YM, Mosina VA, Budagova KR et al. Resistance of Ehrlich tumor cells to apoptosis can be due to accumulation of heat shock proteins. FEBS Lett 1995; 375: 21-26.
37. Gabai VL, Meriin AB, Mosser DD, Caron AW, Rits S, Shifrin VI et al. HSP70 prevent activation of stress kinases: a novel pathway of cellular thermotolerance. J Biol Chem 1997; 272: 18033-18037.
38. Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol 1997; 17: 5317-5327.
39. Hanahan D, Weinberg Robert A. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674.
40. Schmitt E, Maingret L, Puig P-E, Rerole A-L, Ghiringhelli F, Hammann A et al. Heat shock protein 70 neutralization exerts potent antitumor effects in animal models of colon cancer and melanoma . Cancer Res 2006; 66: 4191-4197.
41. Rérole A-L, Gobbo J, De Thonel A, Schmitt E, Pais de Barros JP, Hammann A et al. Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy. Cancer Res 2011; 71: 484-495.
42. Gabai VL, Mabuchi K, Mosser DD, Sherman MY. Hsp72 and stress kinase c-jun N-terminal kinase regulate the Bid-dependent pathway in tumor necrosis factorinduced apoptosis. Mol Cell Biol 2002; 22: 3415-3424.
43. Stankiewicz AR, Lachapelle G, Foo CPZ, Radicioni SM, Mosser DD. Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing bax translocation. J Biol Chem 2005; 280: 38729-38739.
44. Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T et al. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2000; 2: 469-475.
45. Afanasyeva EA, Komarova EY, Larsson L-G, Bahram F, Margulis BA, Guzhova IV. Drug-induced Myc-mediated apoptosis of cancer cells is inhibited by stress protein Hsp70. Int J Cancer 2007; 121: 2615-2621.
46. Nylandsted J, Rohde M, Brand K, Bastholm L, Elling F, Jaattela M. 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 2000; 97: 7871-7876.
47. Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Hoyer-Hansen M et al. Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med 2004; 200: 425-435.
48. Nylandsted J, Wick W, Hirt UA, Brand K, Rohde M, Leist M et al. Eradication of glioblastoma, and breast and colon carcinoma xenografts by Hsp70 depletion. Cancer Res 2002; 62: 7139-7142.
49. Murphy ME. The HSP70 family and cancer. Carcinogenesis 2013; 34: 1181-1188.
50. Powers MV, Jones K, Barillari C, Westwood I, Montfort RLMv, Workman P. Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle 2010; 9: 1542-1550.
51. Collado M, Serrano M. The power and the promise of oncogene-induced senescence markers. Nat Rev Cancer 2006; 6: 472-476.
52. Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J et al. Senescenceassociated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6: 2853-2868.
53. Raulet DH, Guerra N. Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nat Rev Immunol 2009; 9: 568-580.
54. Braig M, Schmitt CA. Oncogene-Induced senescence: putting the brakes on tumor development. Cancer Res 2006; 66: 2881-2884.
55. Gabai VL, Yaglom JA, Waldman T, Sherman MY. Heat shock protein Hsp72 controls oncogene-induced senescence pathways in cancer cells. Mol Cell Biol 2009; 29: 559-569.
56. Yaglom JA, Gabai VL, Sherman MY. High Levels of heat shock protein Hsp72 in cancer cells suppress default senescence pathways. Cancer Res 2007; 67: 2373-2381.
57. Meng L, Hunt C, Yaglom JA, Gabai VL, Sherman MY. Heat shock protein Hsp72 plays an essential role in Her2-induced mammary tumorigenesis. Oncogene 2011; 30: 2836-2845.
58. Dodd K, Nance S, Quezada M, Janke L, Morrison JB, Williams RT et al. Tumorderived inducible heat-shock protein 70 (HSP70) is an essential component of anti-tumor immunity. Oncogene 2015; 34: 1312-1322.
59. Goodwin EC, DiMaio D. Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proc Natl Acad Sci USA 2000; 97: 12513-12518.
60. Weng D, Penzner J, Song B, Koido S, Calderwood S, Gong J. Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers. Breast Cancer Res 2012; 14: R18.
61. Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR. Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 2006; 31: 164-172.
62. Partida-Rodríguez O, Torres J, Flores-Luna L, Camorlinga M, Nieves-Ramírez M, Lazcano E et al. Polymorphisms in TNF and HSP-70 show a significant association with gastric cancer and duodenal ulcer. Int J Cancer 2010; 126: 1861-1868.
63. Szondy K, Rusai K, Szabó AJ, Nagy A, Gal K, Fekete A et al. Tumor cell expression of heat shock protein (HSP) 72 is influenced by HSP72 [HSPA1B A(1267)G] polymorphism and predicts survival in small cell lung cancer (SCLC) patients. Cancer Invest 2012; 30: 317-322.
64. Wang Y, Zhou F, Wu Y, Xu D, Li W, Liang S. The relationship between three heat shock protein 70 gene polymorphisms and susceptibility to lung cancer. Clin Chem Lab Med 2010; 48: 1657.
65. Ciocca D, Arrigo A, Calderwood S. Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update. Arch Toxicol 2013; 87: 19-48.
66. Kabakov AE, Gabai VL. Heat Shock proteins and Cytoprotection: ATP-deprived Mammalian Cells. R.G. Landes Co: Austin, TX, USA, 1997.
67. Kabakov AE, Molotkov AO, Budagova KR, Makarova YuM, Mosin AF, Gabai VL. Adaptation of Ehrlich ascites carcinoma cells to energy deprivation in vivo can be associated with heat shock protein accumulation. J Cell Physiol 1995; 165: 1-6.
68. Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy: oncogene and nononcogene addiction. Cell 2009; 136: 823-837.
69. Torres EM, Sokolsky T, Tucker CM, Chan LY, Boselli M, Dunham MJ et al. Effects of aneuploidy on cellular physiology and cell division in haploid yeast. Science 2007; 317: 916-924.
70. Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, Florens L et al. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature 2010; 468: 321-325.
71. Tang Y-C, Williams BR, Siegel JJ, Amon A. Identification of aneuploidy-selective antiproliferation compounds. Cell 2011; 144: 499-512.
72. Colvin TA, Gabai VL, Sherman MY. Proteotoxicity is not the reason for the dependence of cancer cells on the major chaperone Hsp70. Cell Cycle 2014; 13: 2306-2310.
73. O'Callaghan-Sunol C, Gabai VL, Sherman MY. Hsp27 modulates p53 signaling and suppresses cellular senescence. Cancer Res 2007; 67: 11779-11788.
74. Menssen A, Hermeking H. Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Proc Natl Acad Sci USA 2002; 99: 6274-6279.
75. Myers SM, Mulligan LM. The RET receptor is linked to stress response pathways. Cancer Res 2004; 64: 4453-4463.
76. Ray S, Lu Y, Kaufmann SH, Gustafson WC, Karp JE, Boldogh I et al. 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 2004; 279: 35604-35615.
77. Khaleque M, Bharti A, Sawyer D, Gong J, Benjamin IJ, Stevenson MA et al. Induction of heat shock proteins by heregulin beta1 leads to protection from apoptosis and anchorage-independent growth. Oncogene 2005; 24: 6564-6573.
78. Chou SD, Prince T, Gong J, Calderwood SK. mTOR is essential for the proteotoxic stress response, HSF1 activation and heat shock protein synthesis. PLoS ONE 2012; 7: e39679.
79. McCubrey JA, Steeman L, Chappell W, Abrams S, Montalto G, Cervello M et al. Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget 2012; 3: 954-987.
80. Li D, Yallowitz A, Ozog L, Marchenko N. A gain-of-function mutant p53-HSF1 feed forward circuit governs adaptation of cancer cells to proteotoxic stress. Cell Death Dis 2014; 5: e1194.
81. Yaglom J, O'Callaghan-Sunol C, Gabai V, Sherman MY. Inactivation of dualspecificity phosphatases is involved in the regulation of extracellular signalregulated kinases by heat shock and Hsp72. Mol Cell Biol 2003; 23: 3813-3824.
82. Chung J, Nguyen A-K, Henstridge DC, Holmes AG, Chan MHS, Mesa JL et al. HSP72 protects against obesity-induced insulin resistance. Proc Natl Acad Sci USA 2008; 105: 1739-1744.
83. Colvin TA, Gabai VL, Gong J, Calderwood SK, Li H, Gummuluru S et al. Hsp70-Bag3 module regulates cancer-related signaling networks. Cancer Res 2014; 74: 4731-4740.
84. Wandinger SK, Richter K, Buchner J. The Hsp90 chaperone machinery. J Biol Chem 2008; 283: 18473-18477.
85. Powers MV, Clarke PA, Workman P. Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer Cell 2008; 14: 250-262.
86. Rodina A, Patel Pallav D, Kang Y, Patel Y, Baaklini I, Wong Michael JH et al. Identification of an allosteric pocket on human Hsp70 reveals a mode of inhibition of this therapeutically important protein. Chem Biol 2013; 20: 1469-1480.
87. Song J, Takeda M, Morimoto RI. Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth. Nat Cell Biol 2001; 3: 276-282.
88. Takayama S, Reed JC. Molecular chaperone targeting and regulation by BAG family proteins. Nat Cell Biol 2001; 3: E237-E241.
89. Ingham RJ, Colwill K, Howard C, Dettwiler S, Lim CSH, Yu J et al. WW domains provide a platform for the assembly of multiprotein networks. Mol Cell Biol 2005; 25: 7092-7106.
90. Li SS-C. Specificity and versatility of SH3 and other proline-recognition domains: structural basis and implications for cellular signal transduction. Biochem J 2005; 390: 641-653.
91. Iwasaki M, Homma S, Hishiya A, Dolezal SJ, Reed JC, Takayama S. BAG3 regulates motility and adhesion of epithelial cancer cells. Cancer Res 2007; 67: 10252-10259.
92. Festa M, Del Valle L, Khalili K, Franco R, Scognamiglio G, Graziano V et al. BAG3 protein is overexpressed in human glioblastoma and is a potential target for therapy. Am J Pathol 2011; 178: 2504-2512.
93. Guerriero L, Chong K, Franco R, Rosati A, De Caro F, Capunzo M et al. BAG3 protein expression in melanoma metastatic lymph nodes correlates with patients/' survival. Cell Death Dis 2014; 5: e1173.
94. Franco R, Scognamiglio G, Salerno V, Sebastiani A, Cennamo G, Ascierto PA et al. Expression of the anti-apoptotic protein BAG3 in human melanomas. J Invest Dermatol 2012; 132: 252-254.
95. Rosati A, Bersani S, Tavano F, Dalla Pozza E, De Marco M, Palmieri M et al. Expression of the antiapoptotic protein BAG3 is a feature of pancreatic adenocarcinoma and its overexpression is associated with poorer survival. Am J Pathol 2012; 181: 1524-1529.
96. Liao Q, Ozawa F, Friess H, Zimmermann A, Takayama S, Reed JC et al. The antiapoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines. FEBS Lett 2001; 503: 151-157.
97. Chuma M, Sakamoto N, Nakai A, Hige S, Nakanishi M, Natsuizaka M et al. Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor-κB/mitogen-activated protein kinase. Carcinogenesis 2014; 35: 272-281.
98. Falco A, Rosati A, Festa M, Basile A, De Marco M, d'Avenia M et al. BAG3 is a novel serum biomarker for pancreatic adenocarcinomas. Am J Gastroenterol 2013; 108: 1178-1180.
99. Rosati A, Ammirante M, Gentilella A, Basile A, Festa M, Pascale M et al. Apoptosis inhibition in cancer cells: a novel molecular pathway that involves BAG3 protein. Int J Biochem Cell Biol 2007; 39: 1337-1342.
100. Kassis JN, Guancial EA, Doong H, Virador V, Kohn EC. CAIR-1/BAG-3 modulates cell adhesion and migration by downregulating activity of focal adhesion proteins. Exp Cell Res 2006; 312: 2962-2971.
101. Romano MF, Festa M, Petrella A, Pascale M, Bisogni R, Poggi V et al. BAG3 protein regulates cell survival in childhood acute lymphoblastic leukemia cells. Cancer Biol Ther 2003; 2: 508-510.
102. Romano MF, Festa M, Pagliuca G, Lerose R, Bisogni R, Chiurazzi F et al. BAG3 protein controls B-chronic lymphocytic leukaemia cell apoptosis. Cell Death Differ 2003; 10: 383-385.
103. Franceschelli S, Rosati A, Lerose R, De Nicola S, Turco MC, Pascale M. bag3 gene expression is regulated by heat shock factor 1. J Cell Physiol 2008; 215: 575-577.
104. Gamerdinger M, Carra S, Behl C. Emerging roles of molecular chaperones and cochaperones in selective autophagy: focus on BAG proteins. J Mol Med 2011; 89: 1175-1182.
105. Gamerdinger M, Kaya AM, Wolfrum U, Clement AM, Behl C. BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep 2011; 12: 149-156.
106. Ulbricht A, Eppler Felix J, Tapia Victor E, van der Ven Peter FM, Hampe N, Hersch N et al. Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy. Curr Biol 2013; 23: 430-435.
107. Zhang J, Ji J-Y, Yu M, Overholtzer M, Smolen GA, Wang R et al. YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nat Cell Biol 2009; 11: 1444-1450.
108. Mo JS, Park HW, Guan KL. The Hippo signaling pathway and stem cell biology. Trends Cell Biol 2014; 22: 339-346.
109. Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA et al. CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70. Oncogene 2000; 19: 4385-4395.
110. Tsukahara F, Maru Y. Bag1 directly routes immature BCR-ABL for proteasomal degradation. Blood 2010; 116: 3582-3592.
111. Leznicki P, Roebuck QP, Wunderley L, Clancy A, Krysztofinska EM, Isaacson RL et al. The association of BAG6 with SGTA and tail-anchored proteins. PLoS ONE 2013; 8: e59590.
112. Assimon VA, Gillies AT, Rauch JN, Gestwicki JE. Hsp70 protein complexes as drug targets. Curr Pharm Des 2013; 19: 404-417.
113. Patury S, Miyata Y, Gestwicki JE. Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem 2009; 9: 1337-1351.
114. Strom E, Sathe S, Komarov PG, Chernova OB, Pavlovska I, Shyshynova I et al. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol 2006; 2: 474-479.
115. Leu JIJ, Pimkina J, Frank A, Murphy ME, George DL. A small molecule inhibitor of inducible heat shock pProtein 70. Mol Cell 2009; 36: 15-27.
116. Balaburski GM, JI-J Leu, Beeharry N, Hayik S, Andrake MD, Zhang G et al. A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res 2013; 11: 219-229.
117. Koren J III, Miyata Y, Kiray J, O'Leary JC III, Nguyen L, Guo J et al. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance. PLoS ONE 2012; 7: e35566.
118. Rousaki A, Miyata Y, Jinwal UK, Dickey CA, Gestwicki JE, Zuiderweg ERP. Allosteric drugs: the interaction of antitumor compound MKT-077 with human Hsp70 chaperones. J Mol Biol 2011; 411: 614-632.
119. Wang AM, Miyata Y, Klinedinst S, Peng H-M, Chua JP, Komiyama T et al. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol 2013; 9: 112-118.
120. Miyata Y, Li X, Lee H-F, Jinwal UK, Srinivasan SR, Seguin SP et al. Synthesis and initial evaluation of YM-08, a blood-brain barrier permeable derivative of the heat shock protein 70 (Hsp70) inhibitor MKT-077, which reduces tau levels. ACS Chem Neurosci 2013; 4: 930-939.
121. Wiech M, Olszewski MB, Tracz-Gaszewska Z, Wawrzynow B, Zylicz M, Zylicz A. Molecular mechanism of mutant p53 stabilization: the role of HSP70 and MDM2. PLoS ONE 2012; 7: e51426.
122. Muller P, Hrstka R, Coomber D, Lane DP, Vojtesek B. Chaperone-dependent stabilization and degradation of p53 mutants. Oncogene 2008; 27: 3371-3383.
123. Walerych D, Olszewski MB, Gutkowska M, Helwak A, Zylicz M, Zylicz A. Hsp70 molecular chaperones are required to support p53 tumor suppressor activity under stress conditions. Oncogene 2009; 28: 4284-4294.
124. Massey A, Williamson D, Browne H, Murray J, Dokurno P, Shaw T et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol 2010; 66: 535-545.
125. Chang L, Miyata Y, Ung PMU, Bertelsen EB, McQuade TJ, Carlson HA et al. Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem Biol 2011; 18: 210-221.
126. Vos MJ, Hageman J, Carra S, Kampinga HH. Structural and functional diversities between members of the human HSPB, HSPH, HSPA, and DNAJ chaperone families. Biochemistry 2008; 47: 7001-7011.
127. Phillips PA, Sangwan V, Borja-Cacho D, Dudeja V, Vickers SM, Saluja AK. Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett 2011; 308: 181-188.
128. Lu J, Papp LV, Fang J, Rodriguez-Nieto S, Zhivotovsky B, Holmgren A. Inhibition of mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. Cancer Res 2006; 66: 4410-4418.
129. López-Lázaro M, Martín-Cordero C, Toro MV, Ayuso MJ. Flavonoids as DNA topoisomerase I poisons. J Enzyme Inhib Med Chem 2002; 17: 25-29.
130. Chen D, Daniel KG, Chen MS, Kuhn DJ, Landis-Piwowar KR, Dou QP. Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem Pharmacol 2005; 69: 1421-1432.
131. Huryn DM, Brodsky JL, Brummond KM, Chambers PG, Eyer B, Ireland AW et al. Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators. Proc Nat Acad Sci USA 2011; 108: 6757-6762.
132. Braunstein MJ, Scott SS, Scott CM, Behrman S, Walter P, Wipf P et al. Antimyeloma effects of the heat shock protein 70 molecular chaperone inhibitor MAL3-101. J Oncol 2011; 2011: 232037.
133. Adam C, Baeurle A, Brodsky JL, Wipf P, Schrama D, Becker JC et al. The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma. PLoS ONE 2014; 9: e92041.
134. Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 2012; 18: 64-76.
135. Zou JY, Guo YL, Guettouche T, Smith DF, Voellmy R. Repression of heat shock transcription factor Hsf1 activation by Hsp90 (Hsp90 complex) that forms a stress-sensitive complex with Hsf1. Cell 1998; 94: 471-480.
136. Zaarur NG, Porco VL, Calderwood J, Sherman S, Targeting M. Heat shock response to sensitize cancer cell to proteasome and Hsp90 inhibitors. Cancer Res 2006; 66: 1783-1791.
137. Miyata Y, Rauch Jennifer N, Jinwal Umesh K, Thompson Andrea D, Srinivasan S, Dickey Chad A et al. Cysteine reactivity distinguishes redox sensing by the heatinducible and constitutive forms of heat shock protein 70. Chem Biol 2012; 19: 1391-1399.
138. Koren J, Jinwal UK, Jin Y, O'Leary J, Jones JR, Johnson AG et al. Facilitating Akt clearance via manipulation of Hsp70 activity and levels. J Biol Chem 2010; 285: 2498-2505.