Advanced search×

Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells.

Susanne S Vidot, James J Witham, Roshan R Agarwal, Sebastian S Greenhough, Harnoor S HS Bamrah, Gabor J GJ Tigyi, Stanley B SB Kaye, and Alan A Richardson

Cell Signal 22(6):926-35 (2010) PMID 20100569

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 When serum was withdrawn to remove exogenous LPA, ccPA caused a pronounced potentiation of apoptosis induced by carboplatin in cells expressing autotaxin.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 results indicate that autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells.

Copyright © 2010 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.cellsig.2010.01.017
Version: za2963e q8za1 q8zb6 q8zcb q8zd2 q8zea q8zf2 q8zg8

Similar articles you may find interesting…

  1. Autotaxin: a secreted autocrine/paracrine factor that promotes glioma invasion.
    Dominique B Hoelzinger, Mitsutoshi Nakada, ... Michael E Berens

    J Neurooncol 86(3):297-309 (2008) PMID 17928955

    Glioblastoma multiforme (GBM) is inherently invasive, and it is from the invasive cell population that the tumor recurs. The GBM invasion transcriptome reveals over-expression of various autocrine factors that could act as motility drivers, such as autotaxin (ATX). Some of these factors could also h...
  2. HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3' untranslat...
    L B LB Nabors, G Y GY Gillespie, ... P H PH King

    Cancer Res 61(5):2154-61 (2001) PMID 11280780

    We analyzed and compared the expression pattern of HuR in 35 freshly resected and cultured CNS tumors to determine whether there was any correlation with tumor grade or histological type. We found that HuR mRNA was consistently expressed in all of the tumors, regardless of cell origin or degree of m...
  3. Expression of vascular endothelial growth factor-A and mRNA stability factor HuR in human meningiomas.
    Takahiro T Sakuma, Takao T Nakagawa, ... Toshihiko T Kubota

    J Neurooncol 88(2):143-55 (2008) PMID 18317686

    We studied the expression of vascular endothelial growth factor-A (VEGF-A) and mRNA stability factor HuR in 40 supratentorial meningiomas using RT-PCR, ELISA and immunohistochemistry, and analyzed their associations with the clinicopathological characteristics, including microvascular density (MVD),...