Nuclear GAPDH is vital for hypoxia-induced hepatic stellate cell apoptosis and is indicative of aggressive hepatocellular carcinoma behavior

References

• Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009;27(9):1485–1491. doi:10.1200/JCO.2008.20.775319224838
   PubMed Web of Science ®Google Scholar
• Ji Q, Yang L, Zhou J, et al. Protective effects of paeoniflorin against cobalt chloride-induced apoptosis of endothelial cells via HIF-1alpha pathway. Toxicol In Vitro. 2012;26(3):455–461. doi:10.1016/j.tiv.2012.01.01622269387
   PubMed Web of Science ®Google Scholar
• Ma H, Xie L, Zhang L, et al. Activated hepatic stellate cells promote epithelial-to-mesenchymal transition in hepatocellular carcinoma through transglutaminase 2-induced pseudohypoxia. Commun bio. 2018;1:168. doi:10.1038/s42003-018-0052-430393774
   PubMed Web of Science ®Google Scholar
• Geng ZM, Jha RK, Li B, et al. Sorafenib inhibition of hepatic stellate cell proliferation in tumor microenvironment of hepatocellular carcinoma: a study of the sorafenib mechanisms. Cell Biochem Biophys. 2014;69(3):717–724. doi:10.1007/s12013-014-9858-y24633454
   PubMed Web of Science ®Google Scholar
• Deng J, Huang Q, Wang Y, et al. Hypoxia-inducible factor-1alpha regulates autophagy to activate hepatic stellate cells. Biochem Biophys Res Commun. 2014;454(2):328–334. doi:10.1016/j.bbrc.2014.10.07625450397
   PubMed Web of Science ®Google Scholar
• Carloni V, Luong TV, Rombouts K. Hepatic stellate cells and extracellular matrix in hepatocellular carcinoma: more complicated than ever. Liver Int. 2014;34(6):834–843. doi:10.1111/liv.1246524397349
   PubMed Web of Science ®Google Scholar
• Amann T, Bataille F, Spruss T, et al. Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma. Cancer Sci. 2009;100(4):646–653. doi:10.1111/j.1349-7006.2009.01087.x19175606
   PubMed Web of Science ®Google Scholar
• Liu CH, Chern GJ, Hsu FF, et al. A multifunctional nanocarrier for efficient TRAIL-based gene therapy against hepatocellular carcinoma with desmoplasia in mice. Hepatology. 2018;67(3):899–913. doi:10.1002/hep.2951328885731
   PubMed Web of Science ®Google Scholar
• Sun B, Zhang X, Cheng X, et al. Intratumoral hepatic stellate cells as a poor prognostic marker and a new treatment target for hepatocellular carcinoma. PLoS One. 2013;8(11):e80212. doi:10.1371/journal.pone.008021224278260
   PubMed Web of Science ®Google Scholar
• Nicholls C, Li H, Liu JP. GAPDH: a common enzyme with uncommon functions. Clin Exp Pharmacol Physiol. 2012;39(8):674–679. doi:10.1111/j.1440-1681.2011.05599.x21895736
   PubMed Web of Science ®Google Scholar
• Hara MR, Agrawal N, Kim SF, et al. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol. 2005;7(7):665–674. doi:10.1038/ncb126815951807
   PubMed Web of Science ®Google Scholar
• Hara MR, Thomas B, Cascio MB, et al. Neuroprotection by pharmacologic blockade of the GAPDH death cascade. Proc Natl Acad Sci U S A. 2006;103(10):3887–3889. doi:10.1073/pnas.051132110316505364
   PubMed Web of Science ®Google Scholar
• Oakes D. Antiparkinson efficacy of deprenyl. DATATOP steering committee of Parkinson Study Group. Ann Neurol. 1993;34(4):634. doi:10.1002/(ISSN)1531-82498215256
   PubMedGoogle Scholar
• Zou B, Liu X, Zhang B, et al. The expression of FAP in hepatocellular carcinoma cells is induced by hypoxia and correlates with poor clinical outcomes. J Cancer. 2018;9(18):3278–3286. doi:10.7150/jca.2577530271487
   PubMed Web of Science ®Google Scholar
• Rotterud R, Fossa SD, Nesland JM. Protein networking in bladder cancer: immunoreactivity for FGFR3, EGFR, ERBB2, KAI1, PTEN, and RAS in normal and malignant urothelium. Histol Histopathol. 2007;22(4):349–363. doi:10.14670/HH-22.34917290345
   PubMed Web of Science ®Google Scholar
• Zhou L, Yao LT, Liang ZY, et al. Nuclear translocation of fibroblast growth factor receptor 3 and its significance in pancreatic cancer. Int J Clin Exp Pathol. 2015;8(11):14640–14648.26823787
   PubMed Web of Science ®Google Scholar
• Luo D, Wang Z, Wu J, Jiang C, Wu J. The role of hypoxia inducible factor-1 in hepatocellular carcinoma. Biomed Res Int. 2014;2014:409272. doi:10.1155/2014/40927225101278
   PubMed Web of Science ®Google Scholar
• Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14(7):397–411. doi:10.1038/nrgastro.2017.3828487545
   PubMed Web of Science ®Google Scholar
• Wanka C, Brucker DP, Bahr O, et al. Synthesis of cytochrome C oxidase 2: a p53-dependent metabolic regulator that promotes respiratory function and protects glioma and colon cancer cells from hypoxia-induced cell death. Oncogene. 2012;31(33):3764–3776.22120717
   PubMed Web of Science ®Google Scholar
• Barbini L, Rodriguez J, Dominguez F, Vega F. Glyceraldehyde-3-phosphate dehydrogenase exerts different biologic activities in apoptotic and proliferating hepatocytes according to its subcellular localization. Mol Cell Biochem. 2007;300(1–2):19–28. doi:10.1007/s11010-006-9341-117426931
   PubMed Web of Science ®Google Scholar
• Butera G, Pacchiana R, Mullappilly N, et al. Mutant p53 prevents GAPDH nuclear translocation in pancreatic cancer cells favoring glycolysis and 2-deoxyglucose sensitivity. Biochim Et Biophys Acta Mol Cell Res. 2018;1865(12):1914–1923. doi:10.1016/j.bbamcr.2018.10.005
   PubMed Web of Science ®Google Scholar
• Dando I, Pacchiana R, Pozza ED, et al. UCP2 inhibition induces ROS/Akt/mTOR axis: role of GAPDH nuclear translocation in genipin/everolimus anticancer synergism. Free Radic Biol Med. 2017;113:176–189. doi:10.1016/j.freeradbiomed.2017.09.02228962872
   PubMed Web of Science ®Google Scholar
• Leisner TM, Moran C, Holly SP, Parise LV. CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling. Oncogene. 2013;32(34):4017–4027. doi:10.1038/onc.2012.40822964641
   PubMed Web of Science ®Google Scholar
• Xia YH, Wang ZM, Chen RX, et al. T-cell apoptosis induced by intratumoral activated hepatic stellate cells is associated with lung metastasis in hepatocellular carcinoma. Oncol Rep. 2013;30(3):1175–1184. doi:10.3892/or.2013.257123807027
   PubMed Web of Science ®Google Scholar
• Zhang L, Li Y, Qiao L, Zhao Y, Wei Y, Li Y. Protective effects of hepatic stellate cells against cisplatin-induced apoptosis in human hepatoma G2 cells. Int J Oncol. 2015;47(2):632–640. doi:10.3892/ijo.2015.302426035065
   PubMed Web of Science ®Google Scholar
• Fingas CD, Bronk SF, Werneburg NW, et al. Myofibroblast-derived PDGF-BB promotes Hedgehog survival signaling in cholangiocarcinoma cells. Hepatology. 2011;54(6):2076–2088. doi:10.1002/hep.2458822038837
   PubMed Web of Science ®Google Scholar
• Huang J, Qiu M, Wan L, et al. TGF-beta1 promotes hepatocellular carcinoma invasion and metastasis via ERK pathway-mediated FGFR4 expression. Cellular Physiol Biochem. 2018;45(4):1690–1699. doi:10.1159/00048773729490293
   PubMedGoogle Scholar
• Zhang JY, Zhang F, Hong CQ, et al. Critical protein GAPDH and its regulatory mechanisms in cancer cells. Cancer Biol Med. 2015;12(1):10–22.25859407
   PubMed Web of Science ®Google Scholar
• Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell. 2007;129(7):1261–1274. doi:10.1016/j.cell.2007.06.00917604717
   PubMed Web of Science ®Google Scholar
• Chiche J, Pommier S, Beneteau M, et al. GAPDH enhances the aggressiveness and the vascularization of non-Hodgkin’s B lymphomas via NF-kappaB-dependent induction of HIF-1alpha. Leukemia. 2015;29(5):1163–1176. doi:10.1038/leu.2014.32425394713
   PubMed Web of Science ®Google Scholar
• Gao X, Wang X, Pham TH, et al. NleB, a bacterial effector with glycosyltransferase activity, targets GAPDH function to inhibit NF-kappaB activation. Cell Host Microbe. 2013;13(1):87–99. doi:10.1016/j.chom.2012.11.01023332158
   PubMed Web of Science ®Google Scholar