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Glycerol-3-phosphate acyltransferase 1 promotes tumor cell migration and poor survival in ovarian carcinoma

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 cata...

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Bibliographic Details
Main Authors: Marchan, Rosemarie (Author) , Rempel, Eugen (Author)
Format: Article (Journal)
Language:English
Published: 26 June 2017
In: Cancer research
Year: 2017, Volume: 77, Issue: 17, Pages: 4589-4601
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-16-2065
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1158/0008-5472.CAN-16-2065
Verlag, kostenfrei, Volltext: http://cancerres.aacrjournals.org/content/77/17/4589
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Author Notes:Rosemarie Marchan, Bettina Büttner, Jörg Lambert, Karolina Edlund, Iris Glaeser, Meinolf Blaszkewicz, Gregor Leonhardt, Lisa Marienhoff, Darius Kaszta, Moritz Anft, Carsten Watzl, Katrin Madjar, Marianna Grinberg, Eugen Rempel, Roland Hergenröder, Silvia Selinski, Jörg Rahnenführer, Michaela S. Lesjak, Joanna D. Stewart, Cristina Cadenas, and Jan G. Hengstler
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Summary: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.
Item Description:Gesehen am 20.09.2018
Physical Description:Online Resource
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-16-2065

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