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Review

Heat shock factor 1 (HSF1)-targeted anticancer therapeutics: overview of current preclinical progress

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Pages 369-377 | Received 15 Jan 2019, Accepted 28 Mar 2019, Published online: 07 Apr 2019

References

  • Vihervaara A, Sistonen L. HSF1 at a glance. J Cell Sci. 2014;127:261–266.
  • Lindquist S. The heat-shock response. Ann Rev Biochem. 1986;55:1151–1191.
  • Morimoto RI. The heat shock response: systems biology of proteotoxic stress in aging and disease. Cold Spring Harb Symp Quant Biol. 2011;76:91–99.
  • Prince TL, Kijima T, Tatokoro M, et al. Client proteins and small molecule inhibitors display distinct binding preferences for constitutive and stress-induced HSP90 isoforms and their conformationally restricted mutants. PloS ONE. 2015;10:e0141786.
  • Mendillo ML, Santagata S, Koeva M, et al. HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell. 2012;(150):549–562.
  • Santagata S, Hu R, Lin NU, et al. High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer. Proc Natl Acad Sci U S A. 2011;(108):18378–18383.
  • Liao Y, Xue Y, Zhang L, et al. Higher heat shock factor 1 expression in tumor stroma predicts poor prognosis in esophageal squamous cell carcinoma patients. J Transl Med. 2015;13:338.
  • Dai C, Whitesell L, Rogers AB, et al. Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell. 2007;(130):1005–1018.
  • Alarcon SV, Mollapour M, Lee MJ, et al. Tumor-intrinsic and tumor-extrinsic factors impacting hsp90- targeted therapy. Curr Mol Med. 2012;12:1125–1141.
  • Dai C, Sampson SB. HSF1: guardian of proteostasis in cancer. Trends Cell Biol. 2016;26:17–28.
  • Dai C. The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis. Philos Trans R Soc Lond B Biol Sci. 2018;373:20160525.
  • Littlefield O, Nelson HC. A new use for the ‘wing‘ of the ‘winged‘ helix-turn-helix motif in the HSF-DNA cocrystal. Nat Struct Biol. 1999;6:464–470.
  • Neudegger T, Verghese J, Hayer-Hartl M, et al. Structure of human heat-shock transcription factor 1 in complex with DNA. Nat Struct Mol Biol. 2016;23:140–146.
  • Rabindran SK, Haroun RI, Clos J, et al. Regulation of heat shock factor trimer formation: role of a conserved leucine zipper. Science. 1993;259:230–234.
  • Newton EM, Knauf U, Green M, et al. The regulatory domain of human heat shock factor 1 is sufficient to sense heat stress. Mol Cell Biol. 1996;16:839–846.
  • Budzynski MA, Puustinen MC, Joutsen J, et al. Uncoupling stress-inducible phosphorylation of heat shock factor 1 from its activation. Mol Cell Biol. 2015;35:2530–2540.
  • Shi Y, Kroeger PE, Morimoto RI. The carboxyl-terminal transactivation domain of heat shock factor 1 is negatively regulated and stress responsive. Mol Cell Biol. 1995;15:4309–4318.
  • Green M, Schuetz TJ, Sullivan EK, et al. A heat shock-responsive domain of human HSF1 that regulates transcription activation domain function. Mol Cell Biol. 1995;15:3354–3362.
  • Zuo J, Rungger D, Voellmy R. Multiple layers of regulation of human heat shock transcription factor 1. Mol Cell Biol. 1995;15:4319–4330.
  • Sorger PK, Pelham HR. Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylation. Cell. 1988;54:855–864.
  • Perisic O, Xiao H, Lis JT. Stable binding of Drosophila heat shock factor to head-to-head and tail-to-tail repeats of a conserved 5 bp recognition unit. Cell. 1989;59:797–806.
  • Trinklein ND, Chen WC, Kingston RE, et al. Transcriptional regulation and binding of heat shock factor 1 and heat shock factor 2 to 32 human heat shock genes during thermal stress and differentiation. Cell Stress Chaperones. 2004;9:21–28.
  • Khaleque MA, Bharti A, Gong J, et al. Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1. Oncogene. 2008;27:1886–1893.
  • Zou J, Guo Y, Guettouche T, et al. 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.
  • Conde R, Belak ZR, Nair M, et al. Modulation of Hsf1 activity by novobiocin and geldanamycin. Biochem Cell Biol. 2009;87:845–851.
  • Karagoz GE, Rüdiger SG. Hsp90 interaction with clients. Trends Biochem Sci. 2015;40:117–125.
  • Neef DW, Jaeger AM, Gomez-Pastor R, et al. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1. Cell Rep. 2014;9:955–966.
  • Gidalevitz T, Prahlad V, Morimoto RI. The stress of protein misfolding: from single cells to multicellular organisms. Cold Spring Harb Perspect Biol. 2011;3:a009704.
  • Shi Y, Mosser DD, Morimoto RI. Molecular chaperones as HSF1-specific transcriptional repressors. Genes Dev. 1998;12:654–666.
  • Hentze N, Le Breton L, Wiesner J, et al. Molecular mechanism of thermosensory function of human heat shock transcription factor Hsf1. Elife. 2016;5:e11576.
  • Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet?. Clin Cancer Res. 2012;18:64–76.
  • Trepel J, Mollapour M, Giaccone G, et al. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer. 2010;10:537–549.
  • Johnson ML, Helena AY, Hart EM, et al. Phase I/II study of HSP90 inhibitor AUY922 and erlotinib for EGFR-mutant lung cancer with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. J Clin Oncol. 2015;33:1666–1673.
  • Kijima T, Eguchi T, Neckers L, et al. Monitoring of the heat shock response with a real-time luciferase reporter. Methods Mol Biol. 2018;1709:35–45.
  • Shapiro GI, Kwak E, Dezube BJ, et al. First-in-human phase I dose escalation study of a second-generation non-ansamycin HSP90 inhibitor, AT13387, in patients with advanced solid tumors. Clin Cancer Res. 2015;21:87–97.
  • Do K, Speranza G, Chang LC, et al. Phase I study of the heat shock protein 90 (Hsp90) inhibitor onalespib (AT13387) administered on a daily for 2 consecutive days per week dosing schedule in patients with advanced solid tumors. Invest New Drugs. 2015;33:921–930.
  • Kijima T, Prince TL, Tigue ML, et al. HSP90 inhibitors disrupt a transient HSP90-HSF1 interaction and identify a noncanonical model of HSP90-mediated HSF1 regulation. Sci Rep. 2018;8:6976.
  • Freund A, Zhong FL, Venteicher AS, et al. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014;159:1389–1403.
  • Min JN, Huang L, Zimonjic DB, et al. Selective suppression of lymphomas by functional loss of Hsf1 in a p53-deficient mouse model for spontaneous tumors. Oncogene. 2007;26:5086–5097.
  • Jin X, Moskophidis D, Mivechi NF. Heat shock transcription factor 1 is a key determinant of HCC development by regulating hepatic steatosis and metabolic syndrome. Cell Metab. 2011;14:91–103.
  • Li J, Song P, Jiang T, et al. Heat shock factor 1 epigenetically stimulates glutaminase-1-dependent mTOR activation to promote colorectal carcinogenesis. Mol Ther. 2018;26:1828–1839.
  • Kourtis N, Lazaris C, Hockemeyer K, et al. Oncogenic hijacking of the stress response machinery in T cell acute lymphoblastic leukemia. Nat Med. 2018;24:1157–1166.
  • Gabai VL, Meng L, Kim G, et al. Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR. Mol Cell Biol. 2012;32:929–940.
  • Xi C, Hu Y, Buckhaults P, et al. Heat shock factor Hsf1 cooperates with ErbB2 (Her2/Neu) protein to promote mammary tumorigenesis and metastasis. J Biol Chem. 2012;287:35646–35657.
  • Dai C, Santagata S, Tang Z, et al. Loss of tumor suppressor NF1 activates HSF1 to promote carcinogenesis. J Clin Invest. 2012;122:3742–3754.
  • Meng L, Gabai VL, Sherman MY. Heat-shock transcription factor HSF1 has a critical role in human epidermal growth factor receptor-2-induced cellular transformation and tumorigenesis. Oncogene. 2010;29:5204–5213.
  • Fang F, Chang R, Yang L. Heat shock factor 1 promotes invasion and metastasis of hepatocellular carcinoma in vitro and in vivo. Cancer. 2012;118:1782–1794.
  • Chen Y, Chen J, Loo A, et al. Targeting HSF1 sensitizes cancer cells to HSP90 inhibition. Oncotarget. 2013;4:816–829.
  • Nakamura Y, Fujimoto M, Fukushima S, et al. Heat shock factor 1 is required for migration and invasion of human melanoma in vitro and in vivo. Cancer Lett. 2014;354:329–335.
  • Heimberger T, Andrulis M, Riedel S, et al. The heat shock transcription factor 1 as a potential new therapeutic target in multiple myeloma. Br J Haematol. 2013;160:465–476.
  • Chuma M, Sakamoto N, Nakai A, et al. Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor-kappaB/mitogen-activated protein kinase. Carcinogenesis. 2014;35:272–281.
  • Dudeja V, Chugh RK, Sangwan V, et al. Pro-survival role of heat shock factor 1 in the pathogenesis of pancreatobiliary tumors. Am J Physiol Gastrointest Liver Physiol. 2011;300:G948–955.
  • Zhang CQ, Williams H, Prince TL, et al. Overexpressed HSF1 cancer signature genes cluster in human chromosome 8q. Hum Genomics. 2017;11:35.
  • Gökmen-Polar Y, Badve S. Upregulation of HSF1 in estrogen receptor positive breast cancer. Oncotarget. 2016;7:84239–84245.
  • Engerud H, Tangen IL, Berg A, et al. High level of HSF1 associates with aggressive endometrial carcinoma and suggests potential for HSP90 inhibitors. Br J Cancer. 2014;111:78–84.
  • Björk JK, Ahonen I, Mirtti T, et al. Increased HSF1 expression predicts shorter disease-specific survival of prostate cancer patients following radical prostatectomy. Oncotarget. 2018;9:31200–31213.
  • Scherz-Shouval R, Santagata S, Mendillo ML, et al. The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy. Cell. 2014;158:564–578.
  • Schlessinger A, Liu J, Rost B. Natively unstructured loops differ from other loops. PLoS Comput Biol. 2007;3:e140.
  • Chen H, Liu H, Qing G. Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduct Target Ther. 2018;3:5.
  • Vilaboa N, Boré A, Martin-Saavedra F, et al. New inhibitor targeting human transcription factor HSF1: effects on the heat shock response and tumor cell survival. Nucleic Acids Res. 2017;45:5797–5817.
  • Yoon YJ, Kim JA, Shin KD, et al. KRIBB11 inhibits HSP70 synthesis through inhibition of heat shock factor 1 function by impairing the recruitment of positive transcription elongation factor b to the hsp70 promoter. J Biol Chem. 2011;286:1737–1747.
  • Zhao X, Shi H, Sevilimedu A, et al. An RNA aptamer that interferes with the DNA binding of the HSF transcription activator. Nucleic Acids Res. 2006;34:3755–3761.
  • Acquaviva J, He S, Sang J, et al. mTOR inhibition potentiates HSP90 inhibitor activity via cessation of HSP synthesis. Mol Cancer Res. 2014;12:703–713.
  • Fok JHL, Hedayat S, Zhang L, et al. HSF1 is essential for myeloma cell survival and a promising therapeutic target. Clin Cancer Res. 2018;24:2395–2407.
  • Salamanca HH, Antonyak MA, Cerione RA, et al. Inhibiting heat shock factor 1 in human cancer cells with a potent RNA aptamer. PloS ONE. 2014;9:e96330.
  • Nikotina AD, Koludarova L, Komarova EY, et al. Discovery and optimization of cardenolides inhibiting HSF1 activation in human colon HCT-116 cancer cells. Oncotarget. 2018;9:27268–27279.
  • Zhang D, Zhang B. Selective killing of cancer cells by small molecules targeting heat shock stress response. Biochem Biophys Res Commun. 2016;478:1509–1514.
  • Yokota S, Kitahara M, Nagata K. Benzylidene lactam compound, KNK437, a novel inhibitor of acquisition of thermotolerance and heat shock protein induction in human colon carcinoma cells. Cancer Res. 2000;60:2942–2948.
  • Bustany S, Cahu J, Descamps G, et al. Heat shock factor 1 is a potent therapeutic target for enhancing the efficacy of treatments for multiple myeloma with adverse prognosis. J Hematol Oncol. 2015;8:40.
  • Qi W, White MC, Choi W, et al. Inhibition of inducible heat shock protein-70 (hsp72) enhances bortezomib-induced cell death in human bladder cancer cells. PloS ONE. 2013;8:e69509.
  • Kudryavtsev VA, Khokhlova AV, Mosina VA, et al. Induction of Hsp70 in tumor cells treated with inhibitors of the Hsp90 activity: a predictive marker and promising target for radiosensitization. PloS ONE. 2017;12:e0173640.
  • Kim JA, Lee S, Kim DE, et al. Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter. Carcinogenesis. 2015;36:696–706.
  • Westerheide SD, Kawahara TL, Orton K, et al. Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death. J Biol Chem. 2006;281:9616–9622.
  • Pan J. RNA polymerase—an important molecular target of triptolide in cancer cells. Cancer Lett. 2010;292:149–152.
  • Titov DV, Gilman B, He QL, et al. XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nat Chem Biol. 2011;7:182–188.
  • Leuenroth SJ, Crews CM. Triptolide-induced transcriptional arrest is associated with changes in nuclear substructure. Cancer Res. 2008;68:5257–5266.
  • Phillips PA, Dudeja V, McCarroll JA, et al. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res. 2007;67:9407–9416.
  • Banerjee S, Saluja A. Minnelide, a novel drug for pancreatic and liver cancer. Pancreatology. 2015;15:S39–S43.
  • Isharwal S, Modi S, Arora N, et al. Minnelide inhibits androgen dependent, castration resistant prostate cancer growth by decreasing expression of androgen receptor full length and splice variants. Prostate. 2017;77:584–596.
  • Zaarur N, Gabai VL, Porco JA Jr., et al. Targeting heat shock response to sensitize cancer cells to proteasome and Hsp90 inhibitors. Cancer Res. 2006;66:1783–1791.
  • Schilling D, Kühnel A, Tetzlaff F, et al. NZ28-induced inhibition of HSF1, SP1 and NF-kappaB triggers the loss of the natural killer cell-activating ligands MICA/B on human tumor cells. Cancer Immunol Immunother. 2015;64:599–608.
  • Santagata S, Mendillo ML, Tang YC, et al. Tight coordination of protein translation and HSF1 activation supports the anabolic malignant state. Science. 2013;341:1238303.
  • Basmadjian C, Thuaud F, Ribeiro N, et al. Flavaglines: potent anticancer drugs that target prohibitins and the helicase eIF4A. Future Med Chem. 2013;5:2185–2197.
  • Chou SD, Prince T, Gong J, et al. mTOR is essential for the proteotoxic stress response, HSF1 activation and heat shock protein synthesis. PloS ONE. 2012;7:e39679.
  • Guettouche T, Boellmann F, Lane WS, et al. Analysis of phosphorylation of human heat shock factor 1 in cells experiencing a stress. BMC Biochem. 2005;6:4.
  • Wang X, Grammatikakis N, Siganou A, et al. Regulation of molecular chaperone gene transcription involves the serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of heat shock factor 1. Mol Cell Biol. 2003;23:6013–6026.
  • Wales CT, Taylor FR, Higa AT, et al. ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells. Anticancer Drugs. 2015;26:657–666.
  • Dai S, Tang Z, Cao J, et al. Suppression of the HSF1-mediated proteotoxic stress response by the metabolic stress sensor AMPK. Embo J. 2015;34:275–293.
  • Prince T, Ackerman A, Cavanaugh A, et al. Dual targeting of HSP70 does not induce the heat shock response and synergistically reduces cell viability in muscle invasive bladder cancer. Oncotarget. 2018;9:32702–32717.

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