Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion
Identifieur interne : 000A66 ( Pmc/Curation ); précédent : 000A65; suivant : 000A67Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion
Auteurs : Peter Kreuzaler ; Yulia Panina ; Joanna Segal ; Mariia YunevaSource :
- Molecular Metabolism [ 2212-8778 ] ; 2019.
Abstract
It has been known for close to a century that, on average, tumors have a metabolism that is different from those found in healthy tissues. Typically, tumors show a biosynthetic metabolism that distinguishes itself by engaging in large scale aerobic glycolysis, heightened flux through the pentose phosphate pathway, and increased glutaminolysis among other means. However, it is becoming equally clear that non tumorous tissues at times can engage in similar metabolism, while tumors show a high degree of metabolic flexibility reacting to cues, and stresses in their local environment.
In this review, we want to scrutinize historic and recent research on metabolism, comparing and contrasting oncogenic and physiological metabolic states. This will allow us to better define states of
In our review, we argue that there is not one single oncogenic state, but rather a diverse set of oncogenic states. These are grounded on a physiological proliferative/wound healing program but distinguish themselves due to their large scale of proliferation, mutations, and transcriptional changes in key metabolic pathways, and the adaptations to widespread stress signals within tumors. We find evidence for the necessity of metabolic flexibility and stress responses in tumor progression and how these responses in turn shape oncogenic progression. Lastly, we find evidence for the notion that the metabolic adaptability of tumors frequently frustrates therapeutic interventions.
Url:
DOI: 10.1016/j.molmet.2019.08.021
PubMed: 31668988
PubMed Central: 7056924
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<author><name sortKey="Kreuzaler, Peter" sort="Kreuzaler, Peter" uniqKey="Kreuzaler P" first="Peter" last="Kreuzaler">Peter Kreuzaler</name>
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<author><name sortKey="Panina, Yulia" sort="Panina, Yulia" uniqKey="Panina Y" first="Yulia" last="Panina">Yulia Panina</name>
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<author><name sortKey="Segal, Joanna" sort="Segal, Joanna" uniqKey="Segal J" first="Joanna" last="Segal">Joanna Segal</name>
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<author><name sortKey="Yuneva, Mariia" sort="Yuneva, Mariia" uniqKey="Yuneva M" first="Mariia" last="Yuneva">Mariia Yuneva</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion</title>
<author><name sortKey="Kreuzaler, Peter" sort="Kreuzaler, Peter" uniqKey="Kreuzaler P" first="Peter" last="Kreuzaler">Peter Kreuzaler</name>
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<author><name sortKey="Panina, Yulia" sort="Panina, Yulia" uniqKey="Panina Y" first="Yulia" last="Panina">Yulia Panina</name>
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<author><name sortKey="Segal, Joanna" sort="Segal, Joanna" uniqKey="Segal J" first="Joanna" last="Segal">Joanna Segal</name>
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<author><name sortKey="Yuneva, Mariia" sort="Yuneva, Mariia" uniqKey="Yuneva M" first="Mariia" last="Yuneva">Mariia Yuneva</name>
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<series><title level="j">Molecular Metabolism</title>
<idno type="eISSN">2212-8778</idno>
<imprint><date when="2019">2019</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>It has been known for close to a century that, on average, tumors have a metabolism that is different from those found in healthy tissues. Typically, tumors show a biosynthetic metabolism that distinguishes itself by engaging in large scale aerobic glycolysis, heightened flux through the pentose phosphate pathway, and increased glutaminolysis among other means. However, it is becoming equally clear that non tumorous tissues at times can engage in similar metabolism, while tumors show a high degree of metabolic flexibility reacting to cues, and stresses in their local environment.</p>
</sec>
<sec><title>Scope of the review</title>
<p>In this review, we want to scrutinize historic and recent research on metabolism, comparing and contrasting oncogenic and physiological metabolic states. This will allow us to better define states of <italic>bona fide</italic>
tumor metabolism. We will further contextualize the stress response and the metabolic evolutionary trajectory seen in tumors, and how these contribute to tumor progression. Lastly, we will analyze the implications of these characteristics with respect to therapy response.</p>
</sec>
<sec><title>Major conclusions</title>
<p>In our review, we argue that there is not one single oncogenic state, but rather a diverse set of oncogenic states. These are grounded on a physiological proliferative/wound healing program but distinguish themselves due to their large scale of proliferation, mutations, and transcriptional changes in key metabolic pathways, and the adaptations to widespread stress signals within tumors. We find evidence for the necessity of metabolic flexibility and stress responses in tumor progression and how these responses in turn shape oncogenic progression. Lastly, we find evidence for the notion that the metabolic adaptability of tumors frequently frustrates therapeutic interventions.</p>
</sec>
</div>
</front>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Metab</journal-id>
<journal-id journal-id-type="iso-abbrev">Mol Metab</journal-id>
<journal-title-group><journal-title>Molecular Metabolism</journal-title>
</journal-title-group>
<issn pub-type="epub">2212-8778</issn>
<publisher><publisher-name>Elsevier</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31668988</article-id>
<article-id pub-id-type="pmc">7056924</article-id>
<article-id pub-id-type="publisher-id">S2212-8778(19)30906-8</article-id>
<article-id pub-id-type="doi">10.1016/j.molmet.2019.08.021</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="au1"><name><surname>Kreuzaler</surname>
<given-names>Peter</given-names>
</name>
<xref rid="fn1" ref-type="fn">1</xref>
</contrib>
<contrib contrib-type="author" id="au2"><name><surname>Panina</surname>
<given-names>Yulia</given-names>
</name>
<xref rid="fn1" ref-type="fn">1</xref>
</contrib>
<contrib contrib-type="author" id="au3"><name><surname>Segal</surname>
<given-names>Joanna</given-names>
</name>
<xref rid="fn1" ref-type="fn">1</xref>
</contrib>
<contrib contrib-type="author" id="au4"><name><surname>Yuneva</surname>
<given-names>Mariia</given-names>
</name>
<email>mariia.yuneva@crick.ac.uk</email>
<xref rid="cor1" ref-type="corresp">∗</xref>
</contrib>
</contrib-group>
<aff id="aff1">The Francis Crick Institute, London, UK</aff>
<author-notes><corresp id="cor1"><label>∗</label>
Corresponding author. <email>mariia.yuneva@crick.ac.uk</email>
</corresp>
<fn id="fn1"><label>1</label>
<p id="ntpara0010">These authors contributed equally.</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release"><day>10</day>
<month>10</month>
<year>2019</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection"><month>3</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub"><day>10</day>
<month>10</month>
<year>2019</year>
</pub-date>
<volume>33</volume>
<fpage>83</fpage>
<lpage>101</lpage>
<history><date date-type="received"><day>18</day>
<month>6</month>
<year>2019</year>
</date>
<date date-type="rev-recd"><day>5</day>
<month>8</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>14</day>
<month>8</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© 2019 The Francis Crick Institute</copyright-statement>
<copyright-year>2019</copyright-year>
<license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p>
</license>
</permissions>
<abstract id="abs0010"><sec><title>Background</title>
<p>It has been known for close to a century that, on average, tumors have a metabolism that is different from those found in healthy tissues. Typically, tumors show a biosynthetic metabolism that distinguishes itself by engaging in large scale aerobic glycolysis, heightened flux through the pentose phosphate pathway, and increased glutaminolysis among other means. However, it is becoming equally clear that non tumorous tissues at times can engage in similar metabolism, while tumors show a high degree of metabolic flexibility reacting to cues, and stresses in their local environment.</p>
</sec>
<sec><title>Scope of the review</title>
<p>In this review, we want to scrutinize historic and recent research on metabolism, comparing and contrasting oncogenic and physiological metabolic states. This will allow us to better define states of <italic>bona fide</italic>
tumor metabolism. We will further contextualize the stress response and the metabolic evolutionary trajectory seen in tumors, and how these contribute to tumor progression. Lastly, we will analyze the implications of these characteristics with respect to therapy response.</p>
</sec>
<sec><title>Major conclusions</title>
<p>In our review, we argue that there is not one single oncogenic state, but rather a diverse set of oncogenic states. These are grounded on a physiological proliferative/wound healing program but distinguish themselves due to their large scale of proliferation, mutations, and transcriptional changes in key metabolic pathways, and the adaptations to widespread stress signals within tumors. We find evidence for the necessity of metabolic flexibility and stress responses in tumor progression and how these responses in turn shape oncogenic progression. Lastly, we find evidence for the notion that the metabolic adaptability of tumors frequently frustrates therapeutic interventions.</p>
</sec>
</abstract>
<kwd-group id="kwrds0010"><title>Keywords</title>
<kwd>Tumourigenesis</kwd>
<kwd>Tumour metabolism</kwd>
<kwd>Metabolic flexibility</kwd>
<kwd>Central carbon metabolism</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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