Previously, it has to be acknowledged that overexpressed heat shock protein B27 (HSPB27) have been implicated in the etiology of wide range of human cancers. However, the molecular mechanism leading to the disease initiation to progression in liver cancer is still unknown. Present work was undertaken to investigate the differentially expressed HSPB27 in association with those damages that lead to liver cancer development. For the identification of liver cancer biomarker, samples were subjected to comparative proteomic analysis using two-dimensional gel electrophoresis (2-DE) and were further validated by Western blot and immunohistochemical analysis. After validation, in silico studies were applied to demonstrate the significantly induced phosphorylated and S-nitrosylated signals. The later included the interacting partner of HSPB27, i.e., mitogen-activated protein kinase-3 and 5 (MAPK3 and 5), ubiquitin C (UBC), v-akt murine thymoma viral oncogene homolog 1 (AKT1), mitogen-activated protein kinase 14 (MAPK14), and tumor protein p53 (TP53), which bestowed with critical capabilities, namely, apoptosis, cell cycling, stress activation, tumor suppression, cell survival, angiogenesis, proliferation, and stress resistance. Taking together, these results shed new light on the potential biomarker HSPB27 that overexpression of HSPB27 did lead to upregulation of their interacting partner that together demonstrate their possible role as a novel tumor progressive agent for the treatment of metastasis in liver cancer. HSPB27 is a promising diagnostic marker for liver cancer although further large-scale studies are required. Also, molecular profiling may help pave the road to the discovery of new therapies.
Hepatitis C virus Heat shock protein B27 Two-dimensional gel electrophoresis Western blotting
This is a preview of subscription content, log in to check access
We graciously thank Dr. N. Kabir (Panjwani Center, ICCBS, and University of Karachi- Pakistan) for providing the facility of immunohistochemistry.
The authors also thank Dr. Abid Ali (HEJ, University of Karachi) and Kamran Syed (Chemical House) for providing 2-DE facility. A part of this study was performed at the Industrial Biotechnology Department of The Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Karachi, Pakistan.
Conflicts of interest
RK and MA. R conceived of the study; RK carried out the proteomics studies; EH collected samples and participated in prognosis analysis; NNS assisted in molecular experiments; RK drafted the manuscript; all authors have read and approved the final manuscript.
Arrigo AP. sHsp as novel regulators of programmed cell death and tumorigenicity. Pathol Biol Paris. 2000;48:280–8.PubMedGoogle Scholar
Jolly C, Morimoto RI. Re: role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst. 2001;93:239–40.Google Scholar
van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.CrossRefPubMedGoogle Scholar
Gibert B, Eckel B, Gonin V, Goldschneider D, Fombonne J, Deux B, et al. Targeting heat shock protein 27 (HSPB27) interferes with bone metastasis and tumour formation in vivo. Br J Cancer. 2012;107:63–70.CrossRefPubMedPubMedCentralGoogle Scholar
Lemieux P, Oesterreich S, Lawrence JA, Steeg PS, Hilsenbeck SG, Harvey JM, et al. The small heat shock protein hsp27 increases invasiveness but decreases motility of breast cancer cells. Invasion Metastasis. 1997;17:113–23.PubMedGoogle Scholar
Blackburn RV, Galoforo SS, Berns CM, Armour EP, McEachern D, Corry PM, et al. Comparison of tumor growth between Hsp25- and Hsp27- transfected murine L929 cells in nude mice. Int J Cancer. 1997;72:871–7.CrossRefPubMedGoogle Scholar
Katoh M, Koninkx J, Schumacher U. Heat shock protein expression in human tumours grown in severe combined immunodeficient mice. Cancer Lett. 2000;161:113–20.CrossRefPubMedGoogle Scholar
Hsu HS, Lin JH, Huang WC, et al. Chemoresistance of lung cancer stem like cells depends on activation of Hsp27. Cancer. 2011;117:1516–28.CrossRefPubMedGoogle Scholar
Wei L, Liu TT, Wang HH, et al. Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial-mesenchymal transition and nuclear factor-kappaB. Breast Cancer Res. 2011;13:R101.CrossRefPubMedPubMedCentralGoogle Scholar
Gibert B, Eckel B, Fasquelle L, Moulin M, Bouhallier F, Gonin V, et al. Knock down of heat shock protein 27 (HSPB27) induces degradation of several putative client proteins. PLoS One. 2012;7:e29719.CrossRefPubMedPubMedCentralGoogle Scholar
Arrigo AP, Gibert B. Protein interactomes of three stress inducible small heat shock proteins: HSPB27, HspB5 and HspB8. Int J Hyperth. 2013;29:409–22.CrossRefGoogle Scholar
Arrigo AP. Human small heat shock proteins: protein interactomes of homo- and hetero-oligomeric complexes: an update. FEBS Lett. 2013;587:1959–69.CrossRefPubMedGoogle Scholar
Blum H, Beier H, Gross HJ. Improved silver staining of plant proteins, RNA and DNA in polyacrylamide gels. Electrophoresis. 1987;8:93–9.CrossRefGoogle Scholar
Blom N, Sicheritz-Ponten T, Gupta R, Gammeltoft S, Brunak S. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics. 2004;4:1633–49.CrossRefPubMedGoogle Scholar
Xue Y, Liu Z, Gao X, Jin C, Wen L, Yao X, et al. GPS-SNO: computational prediction of proteins S-nitrosylation sites with a modified GPS alogrithim. PLoS One. 2008;5:e11290.CrossRefGoogle Scholar
Zhang B, Kirov S, Snoddy J. WebGestalt: an integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res. 2005;33:741–8.CrossRefGoogle Scholar
Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, et al. STRING 8-a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res. 2009;37:412–6.CrossRefGoogle Scholar