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Cancer Res. 2017 Sep 1;77(17):4589-4601. doi: 10.1158/0008-5472.CAN-16-2065. Epub 2017 Jun 26.

Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma.

Author information

1
Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Dortmund, Germany. marchan@ifado.de.
2
Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Dortmund, Germany.
3
Interface Processes, Leibniz Institut für Analytische Wissenschaften - ISAS e.V., Dortmund, Germany.
4
Department of Immunology, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany.
5
Department of Statistics, TU Dortmund University, Dortmund, Germany.
6
Center for Organismal Studies, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
7
Division of Cancer Studies, King's College London, London, United Kingdom.
8
University of Southampton, Southampton, United Kingdom.

Abstract

Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth. Cancer Res; 77(17); 4589-601. ©2017 AACR.

PMID:
28652252
DOI:
10.1158/0008-5472.CAN-16-2065
[Indexed for MEDLINE]
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