PP2A deactivation is a common event in oral cancer and reactivation by FTY720 shows promising therapeutic potential

Journal of Cellular Physiology
Bharath Kumar VelmuruganYing-Chin Ko

Abstract

Protein phosphatase 2A (PP2A) is a tumor suppressor gene, that has been frequently deactivated in many types of cancer. However, its molecular and clinical relevance in oral squamous cell carcinoma (OSCC) remain unclear. Here we show that, PP2A deactivation is a common event in oral cancer cells and hyperphosphorylation in its tyrosine-307 (Y307) residue contributes to PP2A deactivation. PP2A restoration by FTY720 treatment reduced cell growth and decreased GSK-3β phosphorylation without significantly altering other PP2A targets. We further detected PP2A phosphorylation in 262 OSCC tissues. Increased expression of p-PP2A in the tumor tissues was significantly correlated with higher N2/N3-stage (aOR = 2.1, 95%CI: 1.2-3.8). Patients with high p-PP2A expression had lower overall survival rates than those with low expression. Hazard ratio analysis showed that, high p-PP2A expression was significantly associated with mortality density (aOR = 2.2, 95%CI: 1.2-4.0) and lower 10-year overall survival (p = 0.027) in lymph node metastasis. However, no interaction was observed between p-PP2A expression and lymph node metastasis. All our results suggest that PP2A is frequently deactivated in oral cancer and determines poor outcome, restorin...Continue Reading

References

Oct 24, 2002·The Journal of Biological Chemistry·Michal HetmanZhengui Xia
Mar 26, 2004·Transplantation Proceedings·B D Kahan
Jan 22, 2005·Current Opinion in Genetics & Development·Veerle JanssensChristine Van Hoof
Jun 30, 2005·International Journal of Cancer. Journal International Du Cancer·Chee-Wai ChuaYong-Chuan Wong
Jul 17, 2007·Cell·Marc Mumby
Jul 17, 2007·Cell·Melissa R JunttilaJukka Westermarck
Mar 11, 2008·Trends in Molecular Medicine·Jukka Westermarck, William C Hahn
Jul 1, 2008·Biochimica Et Biophysica Acta·Pieter J A EichhornRené Bernards
Jan 22, 2010·The New England Journal of Medicine·Jeffrey A CohenUNKNOWN TRANSFORMS Study Group
May 28, 2010·Journal of Cellular Biochemistry·Tongsen ZhengLianxin Liu
Sep 28, 2010·Journal of Surgical Oncology·Matthias KreppelMartin Scheer
Feb 4, 2011·Anti-cancer Agents in Medicinal Chemistry·Peter Kalev, Anna A Sablina
Jun 8, 2011·Future Medicinal Chemistry·Michael VoronkovJeffry B Stock
Jul 6, 2011·Multiple Sclerosis : Clinical and Laboratory Research·X MontalbanL Kappos
Nov 24, 2011·Journal of Cellular Biochemistry·Yan YangShiang Huang
Jan 28, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Aijun LiaoZhuogang Liu
Mar 5, 2013·Cancer Letters·Parthasarathy SeshacharyuluSurinder K Batra
Apr 23, 2013·Chinese Journal of Cancer·Bo WangXu-Dong Wang
May 4, 2013·The Lancet Oncology·Danilo Perrotti, Paolo Neviani
Jan 28, 2014·Annals of Diagnostic Pathology·Li-Sung HsuMaw-Soan Soon
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal

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Citations

Jan 16, 2020·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·Bharath Kumar VelmuruganYing-Chin Ko
Jan 15, 2019·American Journal of Respiratory and Critical Care Medicine·Declan F DohertyPatrick Geraghty
Jul 17, 2018·American Journal of Respiratory Cell and Molecular Biology·Sridesh NathPatrick Geraghty
May 10, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Shu YaoHong Zhou
Jun 23, 2020·European Journal of Pharmacology·Renata Nishida GotoAndreia Machado Leopoldino
Dec 17, 2020·International Journal of Molecular Sciences·Jessica McAnulty, Analisa DiFeo

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