Lysophosphatidic acid activates telomerase in ovarian cancer cells through hypoxia-inducible factor-1α and the PI3K pathway

Kun Yang, Danhua Zheng, Xiaoli Deng, Lin Bai, Yan Xu, Yu Sheng Cong

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Telomerase is reactivated in over 90% of tumors and plays critical roles in tumor progression. The mechanisms by which telomerase is upregulated in cancer cells are poorly understood. Here we showed that a bioactive lipid, lysophophatidic acid (LPA), up-regulated the expression of human telomerase reverse transcriptase (hTERT) and telomerase activity in serous ovarian adenocarcinoma cell lines SKOV3, A2780, and HEY, but not in OCC1, a clear cell ovarian cancer cell line. This cell type specific effect of LPA on telomerase regulation may reflect distinctive genetic backgrounds in different histological subtype of ovarian cancer cells. Our data further suggest that the phosphatidylinositol 3-phosphate kinase (PI3K) pathway and hypoxia-inducible factor-1a (HIF-1a) are likely to be involved in LPA-induced hTERT expression. Targeting human telomerase by LPA is potentially involved in its role of promoting tumor progression.

Original languageEnglish (US)
Pages (from-to)1194-1201
Number of pages8
JournalJournal of Cellular Biochemistry
Volume105
Issue number5
DOIs
StatePublished - Dec 1 2008

Keywords

  • HIF-1α
  • hTERT
  • LPA
  • PI3K/Akt
  • Telomerase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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