Glycolytic suppression dramatically changes the intracellular metabolic profile of multiple cancer cell lines in a mitochondrial metabolism-dependent manner
Identifieur interne : 000733 ( Pmc/Checkpoint ); précédent : 000732; suivant : 000734Glycolytic suppression dramatically changes the intracellular metabolic profile of multiple cancer cell lines in a mitochondrial metabolism-dependent manner
Auteurs : Reika Shiratori ; Kenta Furuichi ; Masashi Yamaguchi ; Natsumi Miyazaki ; Haruna Aoki ; Hiroji Chibana ; Kousei Ito ; Shigeki AokiSource :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
Most cancer cells rely on glycolysis to generate ATP, even when oxygen is available. However, merely inhibiting the glycolysis is insufficient for the eradication of cancer cells. One main reason for this is that cancer cells have the potential to adapt their metabolism to their environmental conditions. In this study, we investigated how cancer cells modify their intracellular metabolism when glycolysis is suppressed, using PANC-1 pancreatic cancer cells and two other solid tumor cell lines, A549 and HeLa. Our study revealed that glycolytically suppressed cells upregulated mitochondrial function and relied on oxidative phosphorylation (OXPHOS) to obtain the ATP necessary for their survival. Dynamic changes in intracellular metabolic profiles were also observed, reflected by the reduced levels of TCA cycle intermediates and elevated levels of most amino acids. Glutamine and glutamate were important for this metabolic reprogramming, as these were largely consumed by influx into the TCA cycle when the glycolytic pathway was suppressed. During the reprogramming process, activated autophagy was involved in modulating mitochondrial function. We conclude that upon glycolytic suppression in multiple types of tumor cells, intracellular energy metabolism is reprogrammed toward mitochondrial OXPHOS in an autophagy-dependent manner to ensure cellular survival.
Url:
DOI: 10.1038/s41598-019-55296-3
PubMed: 31822748
PubMed Central: 6904735
Affiliations:
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University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8675 Japan</nlm:aff><wicri:noCountry code="subfield">Chiba 260-8675 Japan</wicri:noCountry></affiliation></author><author><name sortKey="Furuichi, Kenta" sort="Furuichi, Kenta" uniqKey="Furuichi K" first="Kenta" last="Furuichi">Kenta Furuichi</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0370 1101</institution-id><institution-id institution-id-type="GRID">grid.136304.3</institution-id><institution>Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences,</institution><institution>Chiba University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8675 Japan</nlm:aff><wicri:noCountry code="subfield">Chiba 260-8675 Japan</wicri:noCountry></affiliation></author><author><name sortKey="Yamaguchi, Masashi" sort="Yamaguchi, Masashi" uniqKey="Yamaguchi M" first="Masashi" last="Yamaguchi">Masashi 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University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8675 Japan</nlm:aff><wicri:noCountry code="subfield">Chiba 260-8675 Japan</wicri:noCountry></affiliation></author><author><name sortKey="Aoki, Haruna" sort="Aoki, Haruna" uniqKey="Aoki H" first="Haruna" last="Aoki">Haruna Aoki</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0370 1101</institution-id><institution-id institution-id-type="GRID">grid.136304.3</institution-id><institution>Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences,</institution><institution>Chiba University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8675 Japan</nlm:aff><wicri:noCountry code="subfield">Chiba 260-8675 Japan</wicri:noCountry></affiliation></author><author><name sortKey="Chibana, Hiroji" sort="Chibana, Hiroji" uniqKey="Chibana H" first="Hiroji" last="Chibana">Hiroji Chibana</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0370 1101</institution-id><institution-id institution-id-type="GRID">grid.136304.3</institution-id><institution>Medical Mycology Research Center,</institution><institution>Chiba University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8673 Japan</nlm:aff><wicri:noCountry code="subfield">Chiba 260-8673 Japan</wicri:noCountry></affiliation></author><author><name sortKey="Ito, Kousei" sort="Ito, Kousei" uniqKey="Ito K" first="Kousei" last="Ito">Kousei Ito</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0370 1101</institution-id><institution-id institution-id-type="GRID">grid.136304.3</institution-id><institution>Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences,</institution><institution>Chiba University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8675 Japan</nlm:aff><wicri:noCountry code="subfield">Chiba 260-8675 Japan</wicri:noCountry></affiliation></author><author><name sortKey="Aoki, Shigeki" sort="Aoki, Shigeki" uniqKey="Aoki S" first="Shigeki" last="Aoki">Shigeki Aoki</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0370 1101</institution-id><institution-id institution-id-type="GRID">grid.136304.3</institution-id><institution>Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences,</institution><institution>Chiba University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8675 Japan</nlm:aff><wicri:noCountry code="subfield">Chiba 260-8675 Japan</wicri:noCountry></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Most cancer cells rely on glycolysis to generate ATP, even when oxygen is available. However, merely inhibiting the glycolysis is insufficient for the eradication of cancer cells. One main reason for this is that cancer cells have the potential to adapt their metabolism to their environmental conditions. In this study, we investigated how cancer cells modify their intracellular metabolism when glycolysis is suppressed, using PANC-1 pancreatic cancer cells and two other solid tumor cell lines, A549 and HeLa. Our study revealed that glycolytically suppressed cells upregulated mitochondrial function and relied on oxidative phosphorylation (OXPHOS) to obtain the ATP necessary for their survival. Dynamic changes in intracellular metabolic profiles were also observed, reflected by the reduced levels of TCA cycle intermediates and elevated levels of most amino acids. Glutamine and glutamate were important for this metabolic reprogramming, as these were largely consumed by influx into the TCA cycle when the glycolytic pathway was suppressed. During the reprogramming process, activated autophagy was involved in modulating mitochondrial function. We conclude that upon glycolytic suppression in multiple types of tumor cells, intracellular energy metabolism is reprogrammed toward mitochondrial OXPHOS in an autophagy-dependent manner to ensure cellular survival.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Vander Heiden, Mg" uniqKey="Vander Heiden M">MG Vander Heiden</name></author><author><name sortKey="Cantley, Lc" uniqKey="Cantley L">LC Cantley</name></author><author><name sortKey="Thompson, Cb" uniqKey="Thompson C">CB Thompson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonnet, S" uniqKey="Bonnet S">S Bonnet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Busk, M" uniqKey="Busk M">M Busk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pfeiffer, T" uniqKey="Pfeiffer T">T Pfeiffer</name></author><author><name sortKey="Schuster, S" uniqKey="Schuster S">S 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sortKey="Yamaguchi, M" uniqKey="Yamaguchi M">M Yamaguchi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31822748</article-id><article-id pub-id-type="pmc">6904735</article-id><article-id pub-id-type="publisher-id">55296</article-id><article-id pub-id-type="doi">10.1038/s41598-019-55296-3</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Glycolytic suppression dramatically changes the intracellular metabolic profile of multiple cancer cell lines in a mitochondrial metabolism-dependent manner</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Shiratori</surname><given-names>Reika</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Furuichi</surname><given-names>Kenta</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yamaguchi</surname><given-names>Masashi</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Miyazaki</surname><given-names>Natsumi</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Aoki</surname><given-names>Haruna</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chibana</surname><given-names>Hiroji</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ito</surname><given-names>Kousei</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Aoki</surname><given-names>Shigeki</given-names></name><address><email>aokishigeki@chiba-u.jp</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0370 1101</institution-id><institution-id institution-id-type="GRID">grid.136304.3</institution-id><institution>Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences,</institution><institution>Chiba University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8675 Japan</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0370 1101</institution-id><institution-id institution-id-type="GRID">grid.136304.3</institution-id><institution>Medical Mycology Research Center,</institution><institution>Chiba University,</institution></institution-wrap>Inohana 1-8-1, Chuo-ku, Chiba-city, Chiba 260-8673 Japan</aff></contrib-group><pub-date pub-type="epub"><day>10</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>10</day><month>12</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>9</volume><elocation-id>18699</elocation-id><history><date date-type="received"><day>27</day><month>8</month><year>2019</year></date><date date-type="accepted"><day>26</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2019</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Most cancer cells rely on glycolysis to generate ATP, even when oxygen is available. However, merely inhibiting the glycolysis is insufficient for the eradication of cancer cells. One main reason for this is that cancer cells have the potential to adapt their metabolism to their environmental conditions. In this study, we investigated how cancer cells modify their intracellular metabolism when glycolysis is suppressed, using PANC-1 pancreatic cancer cells and two other solid tumor cell lines, A549 and HeLa. Our study revealed that glycolytically suppressed cells upregulated mitochondrial function and relied on oxidative phosphorylation (OXPHOS) to obtain the ATP necessary for their survival. Dynamic changes in intracellular metabolic profiles were also observed, reflected by the reduced levels of TCA cycle intermediates and elevated levels of most amino acids. Glutamine and glutamate were important for this metabolic reprogramming, as these were largely consumed by influx into the TCA cycle when the glycolytic pathway was suppressed. During the reprogramming process, activated autophagy was involved in modulating mitochondrial function. We conclude that upon glycolytic suppression in multiple types of tumor cells, intracellular energy metabolism is reprogrammed toward mitochondrial OXPHOS in an autophagy-dependent manner to ensure cellular survival.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Cancer metabolism</kwd><kwd>Cancer metabolism</kwd><kwd>Cancer therapy</kwd><kwd>Cancer therapy</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100001700</institution-id><institution>Ministry of Education, Culture, Sports, Science and Technology (MEXT)</institution></institution-wrap></funding-source><award-id>Program for Dissemination of the Tenure-Track System in Japan</award-id><principal-award-recipient><name><surname>Aoki</surname><given-names>Shigeki</given-names></name></principal-award-recipient></award-group></funding-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100001691</institution-id><institution>MEXT | Japan Society for the Promotion of Science (JSPS)</institution></institution-wrap></funding-source><award-id>Grant-in-Aid for Early-Career Scientists (19K16440)</award-id><principal-award-recipient><name><surname>Aoki</surname><given-names>Shigeki</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Aoki, Haruna" sort="Aoki, Haruna" uniqKey="Aoki H" first="Haruna" last="Aoki">Haruna Aoki</name><name sortKey="Aoki, Shigeki" sort="Aoki, Shigeki" uniqKey="Aoki S" first="Shigeki" last="Aoki">Shigeki Aoki</name><name sortKey="Chibana, Hiroji" sort="Chibana, Hiroji" uniqKey="Chibana H" first="Hiroji" last="Chibana">Hiroji Chibana</name><name sortKey="Furuichi, Kenta" sort="Furuichi, Kenta" uniqKey="Furuichi K" first="Kenta" last="Furuichi">Kenta Furuichi</name><name sortKey="Ito, Kousei" sort="Ito, Kousei" uniqKey="Ito K" first="Kousei" last="Ito">Kousei Ito</name><name sortKey="Miyazaki, Natsumi" sort="Miyazaki, Natsumi" uniqKey="Miyazaki N" first="Natsumi" last="Miyazaki">Natsumi Miyazaki</name><name sortKey="Shiratori, Reika" sort="Shiratori, Reika" uniqKey="Shiratori R" first="Reika" last="Shiratori">Reika Shiratori</name><name sortKey="Yamaguchi, Masashi" sort="Yamaguchi, Masashi" uniqKey="Yamaguchi M" first="Masashi" last="Yamaguchi">Masashi Yamaguchi</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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