Phosphatidylcholine-specific phospholipase C activation in epithelial ovarian cancer cells

Francesca Spadaro, Carlo Ramoni, Delia Mezzanzanica, Silvia Miotti, Paola Alberti, Serena Cecchetti, Egidio Iorio, Vincenza Dolo, Silvana Canevari, Franca Podo

Research output: Contribution to journalArticlepeer-review

Abstract

Elucidation of the mechanisms responsible for aberrant phosphatidylcholine (PC) metabolism in cancer cells may allow identification of novel biomarkers of tumor progression and design of new targeted anticancer therapies. We recently reported up-regulation of PC-specific phospholipases in epithelial ovarian cancer cells (EOC) compared with nontumoral (normal or immortalized) counterparts (EONT). In the present study, we focused, in the same cell systems, on levels, subcellular localization, and activity of PC-specific phospholipase C (PC-PLC), for which a key role in cell proliferation, differentiation, and apoptosis has been shown in several mammalian cells. A 66-kDa PC-PLC isoform, detected in nuclear and cytoplasmic compartments of both EOC and EONT cells, accumulated on the external plasma membrane of cancer cells only, where it colocalized with (31 integrin, in nonraft membrane domains. PC-PLC activity was 3-fold higher in total cell lysates and 5-fold higher in membraneenriched fractions of EOC compared with EONT cells. Serum deprivation induced in EOC, but not in EONT, cells a 3-fold decrease in PC-PLC activity, associated with a 40% drop in S-phase fraction. The recovery of both variables to their original levels in serum-restimulated (or lysophosphatidic acid-restimulated) EOC cells was strongly delayed, for at least 24 h, in the presence of the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609). The S-phase of serumrestimulated EONT cells was not sensitive to D609. These findings warrant further investigations on the role of PC-PLC and on the effects of its inhibition on the pathways responsible for constitutive EOC cell stimulation and cell proliferation.

Original languageEnglish
Pages (from-to)6541-6549
Number of pages9
JournalCancer Research
Volume68
Issue number16
DOIs
Publication statusPublished - Aug 15 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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