Heat Shock Protein 27 Phosphorylation State is Associated with Cancer Progression

Overview

Journal Front Genet

Date 2014 Oct 24

PMID 25339975

Citations 66

Authors

Maria Katsogiannou

Claudia Andrieu

Palma Rocchi

Affiliations

Soon will be listed here.

Abstract

Understanding the mechanisms that control stress-induced survival is critical to explain how tumors frequently resist to treatment and to improve current anti-cancer therapies. Cancer cells are able to cope with stress and escape drug toxicity by regulating heat shock proteins (Hsps) expression and function. Hsp27 (HSPB1), a member of the small Hsp family, represents one of the key players of many signaling pathways contributing to tumorigenicity, treatment resistance, and apoptosis inhibition. Hsp27 is overexpressed in many types of cancer and its functions are regulated by post-translational modifications, such as phosphorylation. Protein phosphorylation is the most widespread signaling mechanism in eukaryotic cells, and it is involved in all fundamental cellular processes. Aberrant phosphorylation of Hsp27 has been associated with cancer but the molecular mechanisms by which it is implicated in cancer development and progression remain undefined. This mini-review focuses on the role of phosphorylation in Hsp27 functions in cancer cells and its potential usefulness as therapeutic target in cancer.

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References

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

Tar K, Csortos C, Czikora I, Olah G, Ma S, Wadgaonkar R . Role of protein phosphatase 2A in the regulation of endothelial cell cytoskeleton structure. J Cell Biochem. 2006; 98(4):931-53. DOI: 10.1002/jcb.20829. View

Garrido C . Size matters: of the small HSP27 and its large oligomers. Cell Death Differ. 2002; 9(5):483-5. DOI: 10.1038/sj.cdd.4401005. View

Doppler H, Storz P, Li J, Comb M, Toker A . A phosphorylation state-specific antibody recognizes Hsp27, a novel substrate of protein kinase D. J Biol Chem. 2005; 280(15):15013-9. DOI: 10.1074/jbc.C400575200. View

Cairns J, Qin S, Philp R, Tan Y, Guy G . Dephosphorylation of the small heat shock protein Hsp27 in vivo by protein phosphatase 2A. J Biol Chem. 1994; 269(12):9176-83. View

Wang H, Yang B, Xu C, Wang L, Zhang Y, Xu B . Differential phosphoprotein levels and pathway analysis identify the transition mechanism of LNCaP cells into androgen-independent cells. Prostate. 2009; 70(5):508-17. DOI: 10.1002/pros.21085. View

Lavoie J, Hickey E, Weber L, Landry J . Modulation of actin microfilament dynamics and fluid phase pinocytosis by phosphorylation of heat shock protein 27. J Biol Chem. 1993; 268(32):24210-4. View

Paul C, Simon S, Gibert B, Virot S, Manero F, Arrigo A . Dynamic processes that reflect anti-apoptotic strategies set up by HspB1 (Hsp27). Exp Cell Res. 2010; 316(9):1535-52. DOI: 10.1016/j.yexcr.2010.03.006. View

Guo K, Gan L, Zhang S, Cui F, Cun W, Li Y . Translocation of HSP27 into liver cancer cell nucleus may be associated with phosphorylation and O-GlcNAc glycosylation. Oncol Rep. 2012; 28(2):494-500. DOI: 10.3892/or.2012.1844. View

10.

Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, LUTSCH G, Ducasse C . Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. J Biol Chem. 1999; 274(27):18947-56. DOI: 10.1074/jbc.274.27.18947. View

11.

Clarke J, Mearow K . Cell stress promotes the association of phosphorylated HspB1 with F-actin. PLoS One. 2013; 8(7):e68978. PMC: 3707891. DOI: 10.1371/journal.pone.0068978. View

12.

Watanabe N, Osada H . Phosphorylation-dependent protein-protein interaction modules as potential molecular targets for cancer therapy. Curr Drug Targets. 2012; 13(13):1654-8. DOI: 10.2174/138945012803530035. View

13.

Muller P, Ruckova E, Halada P, Coates P, Hrstka R, Lane D . C-terminal phosphorylation of Hsp70 and Hsp90 regulates alternate binding to co-chaperones CHIP and HOP to determine cellular protein folding/degradation balances. Oncogene. 2012; 32(25):3101-10. DOI: 10.1038/onc.2012.314. View

14.

Havasi A, Li Z, Wang Z, Martin J, Botla V, Ruchalski K . Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem. 2008; 283(18):12305-13. PMC: 2431006. DOI: 10.1074/jbc.M801291200. View

15.

Lopes L, Flynn C, Komalavilas P, Panitch A, Brophy C, Seal B . Inhibition of HSP27 phosphorylation by a cell-permeant MAPKAP Kinase 2 inhibitor. Biochem Biophys Res Commun. 2009; 382(3):535-9. PMC: 2745729. DOI: 10.1016/j.bbrc.2009.03.056. View

16.

Sakai A, Otani M, Miyamoto A, Yoshida H, Furuya E, Tanigawa N . Identification of phosphorylated serine-15 and -82 residues of HSPB1 in 5-fluorouracil-resistant colorectal cancer cells by proteomics. J Proteomics. 2011; 75(3):806-18. DOI: 10.1016/j.jprot.2011.09.023. View

17.

Lambert H, Charette S, Bernier A, Guimond A, Landry J . HSP27 multimerization mediated by phosphorylation-sensitive intermolecular interactions at the amino terminus. J Biol Chem. 1999; 274(14):9378-85. DOI: 10.1074/jbc.274.14.9378. View

18.

Gibert B, Hadchity E, Czekalla A, Aloy M, Colas P, Rodriguez-Lafrasse C . Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers. Oncogene. 2011; 30(34):3672-81. DOI: 10.1038/onc.2011.73. View

19.

Streit U, Reuter H, Bloch W, Wahlers T, Schwinger R, Brixius K . Phosphorylation of myocardial eNOS is altered in patients suffering from type 2 diabetes. J Appl Physiol (1985). 2012; 114(10):1366-74. DOI: 10.1152/japplphysiol.00011.2011. View

20.

Hsu H, Lin J, Huang W, Hsu T, Su K, Chiou S . Chemoresistance of lung cancer stemlike cells depends on activation of Hsp27. Cancer. 2011; 117(7):1516-28. DOI: 10.1002/cncr.25599. View