Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition
Abstract Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling...
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| Veröffentlicht in: | Cancer letters 2017-06, Vol.396, p.117-129 |
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| creator | Halldorsson, Skarphedinn Rohatgi, Neha Magnusdottir, Manuela Choudhary, Kumari Sonal Guðjónsson, Thorarinn Knutsen, Erik Barkovskaya, Anna Hilmarsdottir, Bylgja Perander, Maria Mælandsmo, Gunhild M Gudmundsson, Steinn Rolfsson, Óttar |
| description | Abstract Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination. |
| doi_str_mv | 10.1016/j.canlet.2017.03.019 |
| format | Article |
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Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination.</description><identifier>ISSN: 0304-3835</identifier><identifier>ISSN: 1872-7980</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2017.03.019</identifier><identifier>PMID: 28323032</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Activator protein 1 ; Amino acids ; Bioinformatics ; Biomarkers ; Breast - metabolism ; Breast - pathology ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer ; Cell adhesion & migration ; Cell culture ; Cell survival ; Clinical medical disciplines: 750 ; EMT ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Epithelial-Mesenchymal Transition ; Female ; Genome scale models ; Genomes ; Genotype & phenotype ; Glycolysis ; Hematology, Oncology and Palliative Medicine ; Humans ; Klinisk medisinske fag: 750 ; Medical disciplines: 700 ; Medical prognosis ; Medisinske Fag: 700 ; Mesenchyme ; Metabolism ; Metabolites ; Metabolomics ; Metastases ; Metastasis ; Morphogenesis ; Nodes ; Oncology: 762 ; Onkologi: 762 ; Oxidation ; Peroxisome proliferator-activated receptors ; Transcription factors ; VDP</subject><ispartof>Cancer letters, 2017-06, Vol.396, p.117-129</ispartof><rights>The Author(s)</rights><rights>2017 The Author(s)</rights><rights>Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Limited Jun 28, 2017</rights><rights>info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-870fdb70165f5c2d79db01b7667cacc8bf63e1747a4978784ab9658f6292865a3</citedby><cites>FETCH-LOGICAL-c581t-870fdb70165f5c2d79db01b7667cacc8bf63e1747a4978784ab9658f6292865a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.canlet.2017.03.019$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3536,26546,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28323032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Halldorsson, Skarphedinn</creatorcontrib><creatorcontrib>Rohatgi, Neha</creatorcontrib><creatorcontrib>Magnusdottir, Manuela</creatorcontrib><creatorcontrib>Choudhary, Kumari Sonal</creatorcontrib><creatorcontrib>Guðjónsson, Thorarinn</creatorcontrib><creatorcontrib>Knutsen, Erik</creatorcontrib><creatorcontrib>Barkovskaya, Anna</creatorcontrib><creatorcontrib>Hilmarsdottir, Bylgja</creatorcontrib><creatorcontrib>Perander, Maria</creatorcontrib><creatorcontrib>Mælandsmo, Gunhild M</creatorcontrib><creatorcontrib>Gudmundsson, Steinn</creatorcontrib><creatorcontrib>Rolfsson, Óttar</creatorcontrib><title>Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination.</description><subject>Activator protein 1</subject><subject>Amino acids</subject><subject>Bioinformatics</subject><subject>Biomarkers</subject><subject>Breast - metabolism</subject><subject>Breast - pathology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell culture</subject><subject>Cell survival</subject><subject>Clinical medical disciplines: 750</subject><subject>EMT</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Female</subject><subject>Genome scale models</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Glycolysis</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Klinisk medisinske fag: 750</subject><subject>Medical disciplines: 700</subject><subject>Medical prognosis</subject><subject>Medisinske Fag: 700</subject><subject>Mesenchyme</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Morphogenesis</subject><subject>Nodes</subject><subject>Oncology: 762</subject><subject>Onkologi: 762</subject><subject>Oxidation</subject><subject>Peroxisome proliferator-activated receptors</subject><subject>Transcription factors</subject><subject>VDP</subject><issn>0304-3835</issn><issn>1872-7980</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNqFksFu1DAQhi0EotvCGyCIxIVLwthOYueChCooSEUcgLPlOJPWW8debC_Vvj2OtgXUCyfL9jfzz8w_hLyg0FCg_dttY7R3mBsGVDTAG6DDI7KhUrBaDBIekw1waGsueXdCTlPaAkDXiu4pOWGSMw6cbcjNF8x6DM6aKmJ9a6P1V1WYK5vCFfryOkbUKVe4s_kandWuMuhc5azHVM3BuXC7hvzzn0O1YEJvrg_Leo3aJ5tt8M_Ik1m7hM_vzjPy4-OH7-ef6suvF5_P31_WppM011LAPI2i9NjNnWGTGKYR6Cj6XhhtjBznniMVrdDtIKSQrR6HvpNzzwYm-07zM_LqmNdEm7L1yoeoFQXgQlHeSijEmyOxi-HnHlNWi01rX9pj2CdVhjj0PeUdL-jrB-g27KMv9RdKSsqYaIdCtfeSIaWIs9pFu-h4KLJqtUtt1dEutdqlgKtiVwl7eZd8Py44_Qm696cA744Alnn9shhVMraMFicb0WQ1Bfs_hYcJTLHOGu1u8IDpby8qMQXq27oy68ZQwYHKUsNvhui7yg</recordid><startdate>20170628</startdate><enddate>20170628</enddate><creator>Halldorsson, Skarphedinn</creator><creator>Rohatgi, Neha</creator><creator>Magnusdottir, Manuela</creator><creator>Choudhary, Kumari Sonal</creator><creator>Guðjónsson, Thorarinn</creator><creator>Knutsen, Erik</creator><creator>Barkovskaya, Anna</creator><creator>Hilmarsdottir, Bylgja</creator><creator>Perander, Maria</creator><creator>Mælandsmo, Gunhild M</creator><creator>Gudmundsson, Steinn</creator><creator>Rolfsson, Óttar</creator><general>Elsevier B.V</general><general>Elsevier Limited</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>3HK</scope></search><sort><creationdate>20170628</creationdate><title>Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition</title><author>Halldorsson, Skarphedinn ; Rohatgi, Neha ; Magnusdottir, Manuela ; Choudhary, Kumari Sonal ; Guðjónsson, Thorarinn ; Knutsen, Erik ; Barkovskaya, Anna ; Hilmarsdottir, Bylgja ; Perander, Maria ; Mælandsmo, Gunhild M ; Gudmundsson, Steinn ; Rolfsson, Óttar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c581t-870fdb70165f5c2d79db01b7667cacc8bf63e1747a4978784ab9658f6292865a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Activator protein 1</topic><topic>Amino acids</topic><topic>Bioinformatics</topic><topic>Biomarkers</topic><topic>Breast - metabolism</topic><topic>Breast - pathology</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell culture</topic><topic>Cell survival</topic><topic>Clinical medical disciplines: 750</topic><topic>EMT</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Female</topic><topic>Genome scale models</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Glycolysis</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Klinisk medisinske fag: 750</topic><topic>Medical disciplines: 700</topic><topic>Medical prognosis</topic><topic>Medisinske Fag: 700</topic><topic>Mesenchyme</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Morphogenesis</topic><topic>Nodes</topic><topic>Oncology: 762</topic><topic>Onkologi: 762</topic><topic>Oxidation</topic><topic>Peroxisome proliferator-activated receptors</topic><topic>Transcription factors</topic><topic>VDP</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Halldorsson, Skarphedinn</creatorcontrib><creatorcontrib>Rohatgi, Neha</creatorcontrib><creatorcontrib>Magnusdottir, Manuela</creatorcontrib><creatorcontrib>Choudhary, Kumari Sonal</creatorcontrib><creatorcontrib>Guðjónsson, Thorarinn</creatorcontrib><creatorcontrib>Knutsen, Erik</creatorcontrib><creatorcontrib>Barkovskaya, Anna</creatorcontrib><creatorcontrib>Hilmarsdottir, Bylgja</creatorcontrib><creatorcontrib>Perander, Maria</creatorcontrib><creatorcontrib>Mælandsmo, Gunhild M</creatorcontrib><creatorcontrib>Gudmundsson, Steinn</creatorcontrib><creatorcontrib>Rolfsson, Óttar</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Halldorsson, Skarphedinn</au><au>Rohatgi, Neha</au><au>Magnusdottir, Manuela</au><au>Choudhary, Kumari Sonal</au><au>Guðjónsson, Thorarinn</au><au>Knutsen, Erik</au><au>Barkovskaya, Anna</au><au>Hilmarsdottir, Bylgja</au><au>Perander, Maria</au><au>Mælandsmo, Gunhild M</au><au>Gudmundsson, Steinn</au><au>Rolfsson, Óttar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2017-06-28</date><risdate>2017</risdate><volume>396</volume><spage>117</spage><epage>129</epage><pages>117-129</pages><issn>0304-3835</issn><issn>1872-7980</issn><eissn>1872-7980</eissn><abstract>Abstract Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>28323032</pmid><doi>10.1016/j.canlet.2017.03.019</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Activator protein 1 Amino acids Bioinformatics Biomarkers Breast - metabolism Breast - pathology Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Cell adhesion & migration Cell culture Cell survival Clinical medical disciplines: 750 EMT Epithelial Cells - metabolism Epithelial Cells - pathology Epithelial-Mesenchymal Transition Female Genome scale models Genomes Genotype & phenotype Glycolysis Hematology, Oncology and Palliative Medicine Humans Klinisk medisinske fag: 750 Medical disciplines: 700 Medical prognosis Medisinske Fag: 700 Mesenchyme Metabolism Metabolites Metabolomics Metastases Metastasis Morphogenesis Nodes Oncology: 762 Onkologi: 762 Oxidation Peroxisome proliferator-activated receptors Transcription factors VDP |
| title | Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition |
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