PMID: 25726524Mar 3, 2015Paper

PP2A inhibition determines poor outcome and doxorubicin resistance in early breast cancer and its activation shows promising therapeutic effects

Oncotarget
R RincónF Rojo

Abstract

The protein phosphatase 2A (PP2A) is a key tumor suppressor which has emerged as a novel molecular target in some human cancers. Here, we show that PP2A inhibition is a common event in breast cancer and identified PP2A phosphorylation and deregulation SET and CIP2A as molecular contributing mechanisms to inactivate PP2A. Interestingly, restoration of PP2A activity after FTY720 treatment reduced cell growth, induced apoptosis and decreased AKT and ERK activation. Moreover, FTY720 led to PP2A activation then enhancing doxorubicin-induced antitumor effects both in vitro and in vivo. PP2A inhibition (CPscore: PP2A phosphorylation and/or CIP2A overexpression) was detected in 27% of cases (62/230), and associated with grade (p = 0.017), relapse (p < 0.001), negative estrogen (p < 0.001) and progesterone receptor expression (p < 0.001), HER2-positive tumors (p = 0.049), Ki-67 expression (p < 0.001), and higher AKT (p < 0.001) and ERK (p < 0.001) phosphorylation. Moreover, PP2A inhibition determined shorter overall (p = 0.006) and event-free survival (p = 0.003), and multivariate analysis confirmed its independent prognostic impact. Altogether, our results indicate that PP2A is frequently inactivated in breast cancer and determines wor...Continue Reading

References

Aug 30, 2000·Nature·C M PerouD Botstein
Jan 11, 2005·The Journal of Pathology·D B Longley, P G Johnston
Jan 11, 2005·The Journal of Pathology·Peter T SimpsonSunil R Lakhani
Jun 21, 2005·The Journal of Biological Chemistry·Judith C KeenNancy E Davidson
Sep 21, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lisa M McShaneUNKNOWN Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics
Aug 26, 2006·Biochemical and Biophysical Research Communications·Katsuo Suzuki, Kazuhide Takahashi
Jul 17, 2007·Cell·Marc Mumby
Jan 24, 2008·Cancer Metastasis Reviews·Danilo Perrotti, Paolo Neviani
Feb 8, 2008·Cell Cycle·Melissa R Junttila, Jukka Westermarck
Mar 11, 2008·Trends in Molecular Medicine·Jukka Westermarck, William C Hahn
Dec 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Daniele GeneraliStephen B Fox
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Federico RojoJoan Albanell
Aug 13, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christophe CômeJukka Westermarck
Apr 21, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M Elizabeth H HammondAntonio C Wolff
Jan 19, 2011·FEBS Letters·Yeon A ChoiYoung Yang
Feb 4, 2011·Anti-cancer Agents in Medicinal Chemistry·Peter Kalev, Anna A Sablina
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Oct 1, 2011·Journal of the National Cancer Institute·Mitch DowsettUNKNOWN International Ki-67 in Breast Cancer Working Group
Dec 14, 2011·Breast Cancer Research and Treatment·Yoanne MousseauFranck G Sturtz
Apr 28, 2012·Breast Cancer Research : BCR·Ling-Ming TsengKuen-Feng Chen
Jun 8, 2012·Cancer Biology & Therapy·M Danielle BarefordPaul Dent
May 4, 2013·The Lancet Oncology·Danilo Perrotti, Paolo Neviani
Aug 7, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A GoldhirschUNKNOWN Panel members
Oct 9, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonio C WolffUNKNOWN College of American Pathologists
Mar 5, 2014·The Journal of Cell Biology·Pietri PuustinenMarja Jäättelä
Mar 19, 2014·Clinical Genetics·F B De AbreuG J Tsongalis
Mar 25, 2014·Cancer Biology & Therapy·Giulia MarvasoPierosandro Tagliaferri
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mahnaz JanghorbanRosalie C Sears
Jun 25, 2014·Molecular Cancer·Martina Sj McDermottNorma O'Donovan

❮ Previous
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Citations

Apr 15, 2016·Journal of Experimental & Clinical Cancer Research : CR·Qunying ZhuangZhongning Lin
May 19, 2017·Journal of Cellular Physiology·Bharath K VelmuruganYing-Chin Ko
Jun 29, 2017·Scientific Reports·Satoru KakeKoichi Sato
Dec 22, 2017·Signal Transduction and Targeted Therapy·Xuewen LiuYing Liu
May 4, 2018·Scientific Reports·Evan F GarnerElizabeth A Beierle
Feb 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pengfei LiuYuan Si
Oct 22, 2016·Endocrine-related Cancer·Ion CristóbalJesús García-Foncillas
Jul 27, 2017·Breast Cancer Research and Treatment·Lauren F WattNicole M Verrills
May 27, 2017·Expert Opinion on Therapeutic Targets·Man-Hsin Hung, Kuen-Feng Chen
Jun 20, 2018·The Journal of Pharmacology and Experimental Therapeutics·Chao-Yuan HuangKuen-Feng Chen
Jun 20, 2019·Frontiers in Oncology·Michiel Remmerie, Veerle Janssens
Jun 15, 2020·British Journal of Pharmacology·Ion CristóbalJesús García-Foncillas
Apr 20, 2016·Molecular and Cellular Biology·Ion CristóbalJesús García-Foncillas
Aug 13, 2017·The Biochemical Journal·Matthias DedobbeleerBernard Rogister
Mar 8, 2016·Current Medical Research and Opinion·Ion CristóbalJesús García-Foncillas
Mar 22, 2016·Hepatic Oncology·Josiah Cox, Steven Weinman
Oct 25, 2016·International Journal of Molecular Sciences·Siliang XuShi-Wen Jiang
Aug 23, 2019·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Fei ShenJing Xu
Dec 21, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Henan ZhaoXiaohong Shu
Nov 12, 2017·Pharmacology & Therapeutics·Andrea Huwiler, Uwe Zangemeister-Wittke
Nov 7, 2017·The International Journal of Biochemistry & Cell Biology·Caitlin M O'ConnorGoutham Narla
Oct 23, 2017·Advances in Biological Regulation·Kurt Geffken, Sarah Spiegel

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