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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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2017-09, Vol.77 (17), p.4589-4601 |
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| creator | Marchan, Rosemarie Büttner, Bettina Lambert, Jörg Edlund, Karolina Glaeser, Iris Blaszkewicz, Meinolf Leonhardt, Gregor Marienhoff, Lisa Kaszta, Darius Anft, Moritz Watzl, Carsten Madjar, Katrin Grinberg, Marianna Rempel, Eugen Hergenröder, Roland Selinski, Silvia Rahnenführer, Jörg Lesjak, Michaela S Stewart, Joanna D Cadenas, Cristina Hengstler, Jan G |
| description | 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.
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| doi_str_mv | 10.1158/0008-5472.can-16-2065 |
| format | Article |
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.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.can-16-2065</identifier><identifier>PMID: 28652252</identifier><language>eng</language><publisher>United States: American Association for Cancer Research, Inc</publisher><subject>Acyltransferase ; Animals ; Cell adhesion & migration ; Cell migration ; Cell Movement ; Cell survival ; Choline ; Choline kinase ; Choline Kinase - metabolism ; Enzymes ; Female ; Glycerol ; Glycerol-3-phosphate ; Glycerol-3-Phosphate O-Acyltransferase - metabolism ; Humans ; Kinases ; Lysophosphatidic acid ; Medical prognosis ; Mice ; Mice, Nude ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - enzymology ; Ovarian Neoplasms - mortality ; Ovarian Neoplasms - pathology ; Phosphates ; Prognosis ; Signal Transduction ; Survival Rate ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>Cancer research (Chicago, Ill.), 2017-09, Vol.77 (17), p.4589-4601</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research, Inc. Sep 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-141b8bcabbfc61b827060c00d34ae13b7fcadc3f79991ddf64221e3f67ab5e23</citedby><cites>FETCH-LOGICAL-c450t-141b8bcabbfc61b827060c00d34ae13b7fcadc3f79991ddf64221e3f67ab5e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28652252$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marchan, Rosemarie</creatorcontrib><creatorcontrib>Büttner, Bettina</creatorcontrib><creatorcontrib>Lambert, Jörg</creatorcontrib><creatorcontrib>Edlund, Karolina</creatorcontrib><creatorcontrib>Glaeser, Iris</creatorcontrib><creatorcontrib>Blaszkewicz, Meinolf</creatorcontrib><creatorcontrib>Leonhardt, Gregor</creatorcontrib><creatorcontrib>Marienhoff, Lisa</creatorcontrib><creatorcontrib>Kaszta, Darius</creatorcontrib><creatorcontrib>Anft, Moritz</creatorcontrib><creatorcontrib>Watzl, Carsten</creatorcontrib><creatorcontrib>Madjar, Katrin</creatorcontrib><creatorcontrib>Grinberg, Marianna</creatorcontrib><creatorcontrib>Rempel, Eugen</creatorcontrib><creatorcontrib>Hergenröder, Roland</creatorcontrib><creatorcontrib>Selinski, Silvia</creatorcontrib><creatorcontrib>Rahnenführer, Jörg</creatorcontrib><creatorcontrib>Lesjak, Michaela S</creatorcontrib><creatorcontrib>Stewart, Joanna D</creatorcontrib><creatorcontrib>Cadenas, Cristina</creatorcontrib><creatorcontrib>Hengstler, Jan G</creatorcontrib><title>Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>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.
.</description><subject>Acyltransferase</subject><subject>Animals</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell survival</subject><subject>Choline</subject><subject>Choline kinase</subject><subject>Choline Kinase - metabolism</subject><subject>Enzymes</subject><subject>Female</subject><subject>Glycerol</subject><subject>Glycerol-3-phosphate</subject><subject>Glycerol-3-Phosphate O-Acyltransferase - metabolism</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lysophosphatidic acid</subject><subject>Medical prognosis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - enzymology</subject><subject>Ovarian Neoplasms - mortality</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Phosphates</subject><subject>Prognosis</subject><subject>Signal Transduction</subject><subject>Survival Rate</subject><subject>Tumor Cells, Cultured</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF1PwjAUhhujEUR_gqaJ18V-rN24JIuiCQqJ3DdnXSfDbcV2I-Hfu0Xk6nzkfd-T8yB0z-iUMZk8UUoTIqOYTw00hCnCqZIXaMykSEgcRfISjc-aEboJYdePklF5jUY8UZJzycfoe1EdjfWuIoLsty7st9BaPDfHqvXQhMJ6CBYzvPaudq0NeNPVzuPUVhV-L788tKVrMDQ5Xrt-_9n5Q3mACpcNXh3Al9DgFLwpG1fDLboqoAr27lQnaPPyvElfyXK1eEvnS2IiSVvCIpYlmYEsK4zqWx5TRQ2luYjAMpHFhYHciCKezWYszwsVcc6sKFQMmbRcTNDjX-zeu5_OhlbvXOeb_qJms0T0b8cq7lXyT2W8C8HbQu99WYM_akb1QFgP9PRAT6fzD82UHgj3vodTepfVNj-7_pGKXwkmeEc</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Marchan, Rosemarie</creator><creator>Büttner, Bettina</creator><creator>Lambert, Jörg</creator><creator>Edlund, Karolina</creator><creator>Glaeser, Iris</creator><creator>Blaszkewicz, Meinolf</creator><creator>Leonhardt, Gregor</creator><creator>Marienhoff, Lisa</creator><creator>Kaszta, Darius</creator><creator>Anft, Moritz</creator><creator>Watzl, Carsten</creator><creator>Madjar, Katrin</creator><creator>Grinberg, Marianna</creator><creator>Rempel, Eugen</creator><creator>Hergenröder, Roland</creator><creator>Selinski, Silvia</creator><creator>Rahnenführer, Jörg</creator><creator>Lesjak, Michaela S</creator><creator>Stewart, Joanna D</creator><creator>Cadenas, Cristina</creator><creator>Hengstler, Jan G</creator><general>American Association for Cancer Research, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20170901</creationdate><title>Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma</title><author>Marchan, Rosemarie ; Büttner, Bettina ; Lambert, Jörg ; Edlund, Karolina ; Glaeser, Iris ; Blaszkewicz, Meinolf ; Leonhardt, Gregor ; Marienhoff, Lisa ; Kaszta, Darius ; Anft, Moritz ; Watzl, Carsten ; Madjar, Katrin ; Grinberg, Marianna ; Rempel, Eugen ; Hergenröder, Roland ; Selinski, Silvia ; Rahnenführer, Jörg ; Lesjak, Michaela S ; Stewart, Joanna D ; Cadenas, Cristina ; Hengstler, Jan G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-141b8bcabbfc61b827060c00d34ae13b7fcadc3f79991ddf64221e3f67ab5e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acyltransferase</topic><topic>Animals</topic><topic>Cell adhesion & migration</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell survival</topic><topic>Choline</topic><topic>Choline kinase</topic><topic>Choline Kinase - metabolism</topic><topic>Enzymes</topic><topic>Female</topic><topic>Glycerol</topic><topic>Glycerol-3-phosphate</topic><topic>Glycerol-3-Phosphate O-Acyltransferase - metabolism</topic><topic>Humans</topic><topic>Kinases</topic><topic>Lysophosphatidic acid</topic><topic>Medical prognosis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Ovarian cancer</topic><topic>Ovarian carcinoma</topic><topic>Ovarian Neoplasms - enzymology</topic><topic>Ovarian Neoplasms - mortality</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Phosphates</topic><topic>Prognosis</topic><topic>Signal Transduction</topic><topic>Survival Rate</topic><topic>Tumor Cells, Cultured</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marchan, Rosemarie</creatorcontrib><creatorcontrib>Büttner, Bettina</creatorcontrib><creatorcontrib>Lambert, Jörg</creatorcontrib><creatorcontrib>Edlund, Karolina</creatorcontrib><creatorcontrib>Glaeser, Iris</creatorcontrib><creatorcontrib>Blaszkewicz, Meinolf</creatorcontrib><creatorcontrib>Leonhardt, Gregor</creatorcontrib><creatorcontrib>Marienhoff, Lisa</creatorcontrib><creatorcontrib>Kaszta, Darius</creatorcontrib><creatorcontrib>Anft, Moritz</creatorcontrib><creatorcontrib>Watzl, Carsten</creatorcontrib><creatorcontrib>Madjar, Katrin</creatorcontrib><creatorcontrib>Grinberg, Marianna</creatorcontrib><creatorcontrib>Rempel, Eugen</creatorcontrib><creatorcontrib>Hergenröder, Roland</creatorcontrib><creatorcontrib>Selinski, Silvia</creatorcontrib><creatorcontrib>Rahnenführer, Jörg</creatorcontrib><creatorcontrib>Lesjak, Michaela S</creatorcontrib><creatorcontrib>Stewart, Joanna D</creatorcontrib><creatorcontrib>Cadenas, Cristina</creatorcontrib><creatorcontrib>Hengstler, Jan G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marchan, Rosemarie</au><au>Büttner, Bettina</au><au>Lambert, Jörg</au><au>Edlund, Karolina</au><au>Glaeser, Iris</au><au>Blaszkewicz, Meinolf</au><au>Leonhardt, Gregor</au><au>Marienhoff, Lisa</au><au>Kaszta, Darius</au><au>Anft, Moritz</au><au>Watzl, Carsten</au><au>Madjar, Katrin</au><au>Grinberg, Marianna</au><au>Rempel, Eugen</au><au>Hergenröder, Roland</au><au>Selinski, Silvia</au><au>Rahnenführer, Jörg</au><au>Lesjak, Michaela S</au><au>Stewart, Joanna D</au><au>Cadenas, Cristina</au><au>Hengstler, Jan G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>77</volume><issue>17</issue><spage>4589</spage><epage>4601</epage><pages>4589-4601</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><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.
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| subjects | Acyltransferase Animals Cell adhesion & migration Cell migration Cell Movement Cell survival Choline Choline kinase Choline Kinase - metabolism Enzymes Female Glycerol Glycerol-3-phosphate Glycerol-3-Phosphate O-Acyltransferase - metabolism Humans Kinases Lysophosphatidic acid Medical prognosis Mice Mice, Nude Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - enzymology Ovarian Neoplasms - mortality Ovarian Neoplasms - pathology Phosphates Prognosis Signal Transduction Survival Rate Tumor Cells, Cultured Xenograft Model Antitumor Assays Xenografts |
| title | Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma |
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