Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells.

Cellular Signalling
Susanne VidotAlan Richardson

Abstract

Drug resistance remains a barrier to the effective long term treatment of ovarian cancer. We have established an RNAi-based screen to identify genes which confer resistance to carboplatin or paclitaxel. To validate the screen we showed that siRNA interfering with the apoptosis regulators FLIP and Bcl-X(L) conferred sensitivity to paclitaxel and carboplatin respectively. The expression of 90 genes which have previously been shown to be over-expressed in drug-resistant ovarian cancer was inhibited using siRNA and the impact on sensitivity to carboplatin and paclitaxel was assessed. ENPP2 was identified as a candidate gene causing drug resistance. ENPP2 encodes autotaxin, a phospholipase involved in the synthesis of the survival factor lysophosphatidic acid. siRNA directed to ENPP2 resulted in earlier apoptosis following treatment with carboplatin. 2-carbacyclic phosphatidic acid (ccPA 16:1), a small molecule inhibitor of autotaxin, also accelerated apoptosis induced by carboplatin. Stable ectopic expression of autotaxin in OVCAR-3 cells led to a delay in apoptosis. When serum was withdrawn to remove exogenous LPA, ccPA caused a pronounced potentiation of apoptosis induced by carboplatin in cells expressing autotaxin. These result...Continue Reading

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Citations

Jun 16, 2012·Lipids·Kazuhiro NakamuraYutaka Yatomi
Feb 6, 2014·BMC Cancer·Vijayalakshmi N Ayyagari, Laurent Brard
Jun 26, 2014·Future Medicinal Chemistry·Abby L Parrill
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Feb 25, 2014·FEBS Letters·Matthew G K BeneschDavid N Brindley
Feb 14, 2013·Gynecologic Oncology·Elizabeth RobinsonAlan Richardson
Sep 8, 2012·Biochimica Et Biophysica Acta·David N BrindleyGabor J Tigyi
Aug 26, 2010·British Journal of Pharmacology·Gabor Tigyi
Jan 24, 2014·Biochemical Society Transactions·Elizabeth RobinsonAlan Richardson
Jan 21, 2012·Biochemical Society Transactions·Mari GotohGabor J Tigyi
Jun 6, 2014·ACS Medicinal Chemistry Letters·Natalie FisherAlan Richardson
Mar 8, 2016·PloS One·Vasileios A StamelosAlan Richardson
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ming QuanQian Huang
May 16, 2015·Journal of Lipid Research·Lorenzo FedericoGordon B Mills
Mar 31, 2015·Journal of Lipid Research·Xiaoyun TangDavid N Brindley
Apr 12, 2013·International Journal of Molecular Sciences·Carmen E PyragiusMartin K Oehler
May 26, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guanmin MengDavid N Brindley
Mar 7, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Matthew G K BeneschDavid N Brindley
Jun 14, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Matthew G K BeneschDavid N Brindley
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Apr 20, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Xiaoyun TangDavid N Brindley
Jul 31, 2018·Journal of Medicinal Chemistry·Natalie FisherAlan Richardson

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