Lysophosphatidic acid activates telomerase in ovarian cancer cells through hypoxia-inducible factor-1alpha and the PI3K pathway.
Telomerase is reactivated in over 90% of tumors and plays critical roles in tumor progression. The mechanisms by which telomerase is up-regulated 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-1alpha (HIF-1alpha) 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.
Yang
Kun
K
Key Laboratory for Cell proliferation and Regulation Biology of Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, 19 XinJieKouWai Avenue, Beijing 100875, China.
Zheng
Danhua
D
Deng
Xiaoli
X
Bai
Lin
L
Xu
Yan
Y
Cong
Yu-Sheng
YS
D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008246:Lysophospholipids; D019869:Phosphatidylinositol 3-Kinases; C509186:TERT protein, human; D019098:Telomerase; C032881:lysophosphatidic acid