Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Dec 22

PMID 31861612

Citations 21

Authors

Gaetan Jego

Francois Hermetet

Francois Girodon

Carmen Garrido

Affiliations

Soon will be listed here.

Abstract

While cells from multicellular organisms are dependent upon exogenous signals for their survival, growth, and proliferation, commitment to a specific cell fate requires the correct folding and maturation of proteins, as well as the degradation of misfolded or aggregated proteins within the cell. This general control of protein quality involves the expression and the activity of molecular chaperones such as heat shock proteins (HSPs). HSPs, through their interaction with the STAT3/STAT5 transcription factor pathway, can be crucial both for the tumorigenic properties of cancer cells (cell proliferation, survival) and for the microenvironmental immune cell compartment (differentiation, activation, cytokine secretion) that contributes to immunosuppression, which, in turn, potentially promotes tumor progression. Understanding the contribution of chaperones such as HSP27, HSP70, HSP90, and HSP110 to the STAT3/5 signaling pathway has raised the possibility of targeting such HSPs to specifically restrain STAT3/5 oncogenic functions. In this review, we present how HSPs control STAT3 and STAT5 activation, and vice versa, how the STAT signaling pathways modulate HSP expression. We also discuss whether targeting HSPs is a valid therapeutic option and which HSP would be the best candidate for such a strategy.

Citing Articles

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References

Xu N, Chen Y, Liu W, Chen Y, Fan Z, Liu M . Inhibition of JAK2/STAT3 Signaling Pathway Suppresses Proliferation of Burkitt's Lymphoma Raji Cells via Cell Cycle Progression, Apoptosis, and Oxidative Stress by Modulating HSP70. Med Sci Monit. 2018; 24:6255-6263. PMC: 6140376. DOI: 10.12659/MSM.910170. View

Song D, Chaerkady R, Tan A, Garcia-Garcia E, Nalli A, Suarez-Gauthier A . Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer. Mol Cancer Ther. 2008; 7(10):3275-84. DOI: 10.1158/1535-7163.MCT-08-0508. View

Mahajan N, Whang Y, Mohler J, Earp H . Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res. 2005; 65(22):10514-23. DOI: 10.1158/0008-5472.CAN-05-1127. View

Gray Jr P, Prince T, Cheng J, Stevenson M, Calderwood S . Targeting the oncogene and kinome chaperone CDC37. Nat Rev Cancer. 2008; 8(7):491-5. PMC: 2779120. DOI: 10.1038/nrc2420. View

Nathan D, Lindquist S . Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Mol Cell Biol. 1995; 15(7):3917-25. PMC: 230631. DOI: 10.1128/MCB.15.7.3917. View

Baylot V, Andrieu C, Katsogiannou M, Taieb D, Garcia S, Giusiano S . OGX-427 inhibits tumor progression and enhances gemcitabine chemotherapy in pancreatic cancer. Cell Death Dis. 2011; 2:e221. PMC: 3219088. DOI: 10.1038/cddis.2011.104. View

Kobayashi N, Toyooka S, Soh J, Yamamoto H, Dote H, Kawasaki K . The anti-proliferative effect of heat shock protein 90 inhibitor, 17-DMAG, on non-small-cell lung cancers being resistant to EGFR tyrosine kinase inhibitor. Lung Cancer. 2011; 75(2):161-6. DOI: 10.1016/j.lungcan.2011.04.022. View

Massey A, Williamson D, Browne H, Murray J, Dokurno P, Shaw T . A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 2009; 66(3):535-45. DOI: 10.1007/s00280-009-1194-3. View

Gozzi G, Gonzalez D, Boudesco C, Dias A, Gotthard G, Uyanik B . Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy. Cell Death Differ. 2019; 27(1):117-129. PMC: 7206024. DOI: 10.1038/s41418-019-0343-4. View

10.

Song S, Su Z, Xu H, Niu M, Chen X, Min H . Luteolin selectively kills STAT3 highly activated gastric cancer cells through enhancing the binding of STAT3 to SHP-1. Cell Death Dis. 2017; 8(2):e2612. PMC: 5386483. DOI: 10.1038/cddis.2017.38. View

11.

Calderwood S, Gong J . Heat Shock Proteins Promote Cancer: It's a Protection Racket. Trends Biochem Sci. 2016; 41(4):311-323. PMC: 4911230. DOI: 10.1016/j.tibs.2016.01.003. View

12.

Hanson B, Vesole D . Retaspimycin hydrochloride (IPI-504): a novel heat shock protein inhibitor as an anticancer agent. Expert Opin Investig Drugs. 2009; 18(9):1375-83. DOI: 10.1517/13543780903158934. View

13.

Baxter E, Scott L, Campbell P, East C, Fourouclas N, Swanton S . Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365(9464):1054-61. DOI: 10.1016/S0140-6736(05)71142-9. View

14.

Kosack L, Wingelhofer B, Popa A, Orlova A, Agerer B, Vilagos B . The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease. Cancer Cell. 2019; 35(1):125-139.e9. PMC: 6335503. DOI: 10.1016/j.ccell.2018.11.018. View

15.

Saito Y, Yamagishi N, Hatayama T . Nuclear localization mechanism of Hsp105beta and its possible function in mammalian cells. J Biochem. 2008; 145(2):185-91. DOI: 10.1093/jb/mvn155. View

16.

Shiotsu Y, Neckers L, Wortman I, An W, Schulte T, Soga S . Novel oxime derivatives of radicicol induce erythroid differentiation associated with preferential G(1) phase accumulation against chronic myelogenous leukemia cells through destabilization of Bcr-Abl with Hsp90 complex. Blood. 2000; 96(6):2284-91. View

17.

Echeverria P, Mazaira G, Erlejman A, Gomez-Sanchez C, Piwien Pilipuk G, Galigniana M . Nuclear import of the glucocorticoid receptor-hsp90 complex through the nuclear pore complex is mediated by its interaction with Nup62 and importin beta. Mol Cell Biol. 2009; 29(17):4788-97. PMC: 2725705. DOI: 10.1128/MCB.00649-09. View

18.

Saini J, Sharma P . Clinical, Prognostic and Therapeutic Significance of Heat Shock Proteins in Cancer. Curr Drug Targets. 2017; 19(13):1478-1490. DOI: 10.2174/1389450118666170823121248. View

19.

Lianos G, Alexiou G, Mangano A, Mangano A, Rausei S, Boni L . The role of heat shock proteins in cancer. Cancer Lett. 2015; 360(2):114-8. DOI: 10.1016/j.canlet.2015.02.026. View

20.

Krause S, Gastpar R, Andreesen R, Gross C, Ullrich H, Thonigs G . Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase i trial. Clin Cancer Res. 2004; 10(11):3699-707. DOI: 10.1158/1078-0432.CCR-03-0683. View