Activation of Aurora A kinase increases YAP stability via blockage of autophagy
Identifieur interne : 000A39 ( Pmc/Checkpoint ); précédent : 000A38; suivant : 000A40Activation of Aurora A kinase increases YAP stability via blockage of autophagy
Auteurs : Peng Wang [République populaire de Chine] ; Ying Gong [République populaire de Chine] ; Tao Guo [République populaire de Chine] ; Man Li [République populaire de Chine] ; Lei Fang [République populaire de Chine] ; Shengchen Yin [République populaire de Chine] ; Muhammad Kamran [République populaire de Chine] ; Yang Liu [République populaire de Chine] ; Jie Xu [République populaire de Chine] ; Lingzhi Xu [République populaire de Chine] ; Fei Peng [République populaire de Chine] ; Xiaoyuan Xue [République populaire de Chine] ; Mengying Yang [République populaire de Chine] ; Mie-Chie Hung [États-Unis] ; Eric W.-F. Lam ; Chundong Gu [République populaire de Chine] ; Chunli Wang [République populaire de Chine] ; Qimin Zhan [République populaire de Chine] ; Quentin Liu [République populaire de Chine]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2019.
Abstract
Transcription cofactor Yes-associated protein (YAP) plays an important role in cancer progression. Here, we found that Aurora A kinase expression was positively correlated with YAP in lung cancer. Aurora A depletion suppresses lung cancer cell colony formation, which could be reversed by YAP ectopic overexpression. In addition, activation of Aurora A increases YAP protein abundance through maintaining its protein stability. Consistently, the transcriptional activity of YAP is increased upon Aurora A activation. We further showed that shAURKA suppressed YAP expression in the absence of Lats1/2, indicating that Aurora A regulates YAP independently of Hippo pathway. Instead, Aurora A induced blockage of autophagy to up-regulate YAP expression. Collectively, our findings provide insights into regulatory mechanisms of YAP expression in lung cancer development.
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DOI: 10.1038/s41419-019-1664-4
PubMed: 31160567
PubMed Central: 6547697
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sortKey="Liu, Quentin" sort="Liu, Quentin" uniqKey="Liu Q" first="Quentin" last="Liu">Quentin Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31160567</idno><idno type="pmc">6547697</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547697</idno><idno type="RBID">PMC:6547697</idno><idno type="doi">10.1038/s41419-019-1664-4</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000058</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000058</idno><idno type="wicri:Area/Pmc/Curation">000058</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000058</idno><idno type="wicri:Area/Pmc/Checkpoint">000A39</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A39</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Activation of Aurora A kinase increases YAP stability via blockage of autophagy</title><author><name sortKey="Wang, Peng" sort="Wang, Peng" uniqKey="Wang P" first="Peng" last="Wang">Peng Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The First Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Gong, Ying" sort="Gong, Ying" uniqKey="Gong Y" first="Ying" last="Gong">Ying Gong</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0027 0586</institution-id><institution-id institution-id-type="GRID">grid.412474.0</institution-id><institution>Laboratory of Molecular 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1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The First Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The Second Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Fang, Lei" sort="Fang, Lei" uniqKey="Fang L" first="Lei" last="Fang">Lei Fang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de 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University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Kamran, Muhammad" sort="Kamran, Muhammad" uniqKey="Kamran M" first="Muhammad" last="Kamran">Muhammad Kamran</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Yang" sort="Liu, Yang" uniqKey="Liu Y" first="Yang" last="Liu">Yang Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The First Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Jie" sort="Xu, Jie" uniqKey="Xu J" first="Jie" last="Xu">Jie Xu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Lingzhi" sort="Xu, Lingzhi" uniqKey="Xu L" first="Lingzhi" last="Xu">Lingzhi Xu</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The Second Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Peng, Fei" sort="Peng, Fei" uniqKey="Peng F" first="Fei" last="Peng">Fei Peng</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Xue, Xiaoyuan" sort="Xue, Xiaoyuan" uniqKey="Xue X" first="Xiaoyuan" last="Xue">Xiaoyuan Xue</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Mengying" sort="Yang, Mengying" uniqKey="Yang M" first="Mengying" last="Yang">Mengying Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Hung, Mie Chie" sort="Hung, Mie Chie" uniqKey="Hung M" first="Mie-Chie" last="Hung">Mie-Chie Hung</name><affiliation wicri:level="2"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2291 4776</institution-id><institution-id institution-id-type="GRID">grid.240145.6</institution-id><institution>Department of Molecular and Cellular Oncology,</institution><institution>The University of Texas MD Anderson cancer center,</institution></institution-wrap>Houston, TX 77030 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Texas</region></placeName><wicri:cityArea>Houston</wicri:cityArea></affiliation></author><author><name sortKey="Lam, Eric W F" sort="Lam, Eric W F" uniqKey="Lam E" first="Eric W.-F." last="Lam">Eric W.-F. Lam</name><affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id><institution-id institution-id-type="GRID">grid.7445.2</institution-id><institution>Department of Surgery and Cancer,</institution><institution>Imperial College London, Imperial Centre for Translational and Experimental Medicine (ICTEM),</institution></institution-wrap>Du Cane Road, London, W12 0NN UK</nlm:aff><wicri:noCountry code="subfield">W12 0NN UK</wicri:noCountry></affiliation></author><author><name sortKey="Gu, Chundong" sort="Gu, Chundong" uniqKey="Gu C" first="Chundong" last="Gu">Chundong Gu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The First Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Chunli" sort="Wang, Chunli" uniqKey="Wang C" first="Chunli" last="Wang">Chunli Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author><author><name sortKey="Zhan, Qimin" sort="Zhan, Qimin" uniqKey="Zhan Q" first="Qimin" last="Zhan">Qimin Zhan</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0027 0586</institution-id><institution-id institution-id-type="GRID">grid.412474.0</institution-id><institution>Laboratory of Molecular Oncology,</institution><institution>Peking University Cancer Hospital & Institute,</institution></institution-wrap>Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Quentin" sort="Liu, Quentin" uniqKey="Liu Q" first="Quentin" last="Liu">Quentin Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Dalian</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell Death & Disease</title><idno type="eISSN">2041-4889</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">Transcription cofactor Yes-associated protein (YAP) plays an important role in cancer progression. Here, we found that Aurora A kinase expression was positively correlated with YAP in lung cancer. Aurora A depletion suppresses lung cancer cell colony formation, which could be reversed by YAP ectopic overexpression. In addition, activation of Aurora A increases YAP protein abundance through maintaining its protein stability. Consistently, the transcriptional activity of YAP is increased upon Aurora A activation. We further showed that shAURKA suppressed YAP expression in the absence of Lats1/2, indicating that Aurora A regulates YAP independently of Hippo pathway. Instead, Aurora A induced blockage of autophagy to up-regulate YAP expression. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Cell Death Dis</journal-id><journal-id journal-id-type="iso-abbrev">Cell Death Dis</journal-id><journal-title-group><journal-title>Cell Death & Disease</journal-title></journal-title-group><issn pub-type="epub">2041-4889</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">31160567</article-id><article-id pub-id-type="pmc">6547697</article-id><article-id pub-id-type="publisher-id">1664</article-id><article-id pub-id-type="doi">10.1038/s41419-019-1664-4</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Activation of Aurora A kinase increases YAP stability via blockage of autophagy</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Wang</surname><given-names>Peng</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Gong</surname><given-names>Ying</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name><surname>Guo</surname><given-names>Tao</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Li</surname><given-names>Man</given-names></name><address><phone>+86-411-84671291-6031</phone><email>liman126126@163.com</email></address><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Fang</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Yin</surname><given-names>Shengchen</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kamran</surname><given-names>Muhammad</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Yang</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Jie</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Lingzhi</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Peng</surname><given-names>Fei</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Xue</surname><given-names>Xiaoyuan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Mengying</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-4317-4740</contrib-id><name><surname>Hung</surname><given-names>Mie-Chie</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-1274-3576</contrib-id><name><surname>Lam</surname><given-names>Eric W.-F.</given-names></name><xref ref-type="aff" rid="Aff6">6</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Gu</surname><given-names>Chundong</given-names></name><address><phone>+86-411-83635963-2061</phone><email>chundong2003@163.com</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Wang</surname><given-names>Chunli</given-names></name><address><phone>+86-411-86110511</phone><email>chunly509@hotmail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Zhan</surname><given-names>Qimin</given-names></name><address><phone>+88196735</phone><email>zhanqimin@bjmu.edu.cn</email></address><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Liu</surname><given-names>Quentin</given-names></name><address><phone>+86-411-86110508</phone><email>liuq9@mail.sysu.edu.cn</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 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>Institute of Cancer Stem Cell,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The First Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0027 0586</institution-id><institution-id institution-id-type="GRID">grid.412474.0</institution-id><institution>Laboratory of Molecular Oncology,</institution><institution>Peking University Cancer Hospital & Institute,</institution></institution-wrap>Beijing, China</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9558 1426</institution-id><institution-id institution-id-type="GRID">grid.411971.b</institution-id><institution>The Second Affiliated Hospital,</institution><institution>Dalian Medical University,</institution></institution-wrap>Dalian, China</aff><aff id="Aff5"><label>5</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2291 4776</institution-id><institution-id institution-id-type="GRID">grid.240145.6</institution-id><institution>Department of Molecular and Cellular Oncology,</institution><institution>The University of Texas MD Anderson cancer center,</institution></institution-wrap>Houston, TX 77030 USA</aff><aff id="Aff6"><label>6</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id><institution-id institution-id-type="GRID">grid.7445.2</institution-id><institution>Department of Surgery and Cancer,</institution><institution>Imperial College London, Imperial Centre for Translational and Experimental Medicine (ICTEM),</institution></institution-wrap>Du Cane Road, London, W12 0NN UK</aff></contrib-group><pub-date pub-type="epub"><day>3</day><month>6</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>3</day><month>6</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>6</month><year>2019</year></pub-date><volume>10</volume><issue>6</issue><elocation-id>432</elocation-id><history><date date-type="received"><day>6</day><month>9</month><year>2018</year></date><date date-type="rev-recd"><day>30</day><month>4</month><year>2019</year></date><date date-type="accepted"><day>13</day><month>5</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">Transcription cofactor Yes-associated protein (YAP) plays an important role in cancer progression. Here, we found that Aurora A kinase expression was positively correlated with YAP in lung cancer. Aurora A depletion suppresses lung cancer cell colony formation, which could be reversed by YAP ectopic overexpression. In addition, activation of Aurora A increases YAP protein abundance through maintaining its protein stability. Consistently, the transcriptional activity of YAP is increased upon Aurora A activation. We further showed that shAURKA suppressed YAP expression in the absence of Lats1/2, indicating that Aurora A regulates YAP independently of Hippo pathway. Instead, Aurora A induced blockage of autophagy to up-regulate YAP expression. Collectively, our findings provide insights into regulatory mechanisms of YAP expression in lung cancer development.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Non-small-cell lung cancer</kwd><kwd>Autophagy</kwd><kwd>HIPPO signalling</kwd></kwd-group><funding-group><award-group><funding-source><institution>Innovative Research Team in University of Ministry of Education of China (No. IRT_17R15), National Natural Science Foundation of China (No.81630005 and 81573025 to QL, National Key Research and Development Program of China(2017YFA0505600-04 to QL) and Dalian high-level talent innovation program (2016RD12 to QL)</institution></funding-source></award-group></funding-group><funding-group><award-group><funding-source><institution>E. W.-F. Lam's work is supported by MRC (MR/N012097/1), CRUK (A12011), Breast Cancer Now (2012MayPR070; 2012NovPhD016), the Cancer Research UK Imperial Centre, Imperial ECMC and NIHR Imperial BRC.</institution></funding-source></award-group></funding-group><funding-group><award-group><funding-source><institution>National Natural Science Foundation of China No.81173453 to C-DG</institution></funding-source></award-group></funding-group><funding-group><award-group><funding-source><institution>National Natural Science Foundation of China (No.81402445 to C-LW&&Liaoning Science Fund for Young Scholars(No.5061137 to C-LW)& Financial support by CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences(No.to KL-1706 to C-LW).</institution></funding-source></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><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Texas</li></region></list><tree><noCountry><name sortKey="Lam, Eric W F" sort="Lam, Eric W F" uniqKey="Lam E" first="Eric W.-F." last="Lam">Eric W.-F. Lam</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Peng" sort="Wang, Peng" uniqKey="Wang P" first="Peng" last="Wang">Peng Wang</name></noRegion><name sortKey="Fang, Lei" sort="Fang, Lei" uniqKey="Fang L" first="Lei" last="Fang">Lei Fang</name><name sortKey="Fang, Lei" sort="Fang, Lei" uniqKey="Fang L" first="Lei" last="Fang">Lei Fang</name><name sortKey="Gong, Ying" sort="Gong, Ying" uniqKey="Gong Y" first="Ying" last="Gong">Ying Gong</name><name sortKey="Gong, Ying" sort="Gong, Ying" uniqKey="Gong Y" first="Ying" last="Gong">Ying Gong</name><name sortKey="Gu, Chundong" sort="Gu, Chundong" uniqKey="Gu C" first="Chundong" last="Gu">Chundong Gu</name><name sortKey="Gu, Chundong" sort="Gu, Chundong" uniqKey="Gu C" first="Chundong" last="Gu">Chundong Gu</name><name sortKey="Guo, Tao" sort="Guo, Tao" uniqKey="Guo T" first="Tao" last="Guo">Tao Guo</name><name sortKey="Guo, Tao" sort="Guo, Tao" uniqKey="Guo T" first="Tao" last="Guo">Tao Guo</name><name sortKey="Kamran, Muhammad" sort="Kamran, Muhammad" uniqKey="Kamran M" first="Muhammad" last="Kamran">Muhammad Kamran</name><name sortKey="Li, Man" sort="Li, Man" uniqKey="Li M" first="Man" last="Li">Man Li</name><name sortKey="Liu, Quentin" sort="Liu, Quentin" uniqKey="Liu Q" first="Quentin" last="Liu">Quentin Liu</name><name sortKey="Liu, Yang" sort="Liu, Yang" uniqKey="Liu Y" first="Yang" last="Liu">Yang Liu</name><name sortKey="Peng, Fei" sort="Peng, Fei" uniqKey="Peng F" first="Fei" last="Peng">Fei Peng</name><name sortKey="Wang, Chunli" sort="Wang, Chunli" uniqKey="Wang C" first="Chunli" last="Wang">Chunli Wang</name><name sortKey="Wang, Peng" sort="Wang, Peng" uniqKey="Wang P" first="Peng" last="Wang">Peng Wang</name><name sortKey="Xu, Jie" sort="Xu, Jie" uniqKey="Xu J" first="Jie" last="Xu">Jie Xu</name><name sortKey="Xu, Lingzhi" sort="Xu, Lingzhi" uniqKey="Xu L" first="Lingzhi" last="Xu">Lingzhi Xu</name><name sortKey="Xue, Xiaoyuan" sort="Xue, Xiaoyuan" uniqKey="Xue X" first="Xiaoyuan" last="Xue">Xiaoyuan Xue</name><name sortKey="Yang, Mengying" sort="Yang, Mengying" uniqKey="Yang M" first="Mengying" last="Yang">Mengying Yang</name><name sortKey="Yin, Shengchen" sort="Yin, Shengchen" uniqKey="Yin S" first="Shengchen" last="Yin">Shengchen Yin</name><name sortKey="Zhan, Qimin" sort="Zhan, Qimin" uniqKey="Zhan Q" first="Qimin" last="Zhan">Qimin Zhan</name></country><country name="États-Unis"><region name="Texas"><name sortKey="Hung, Mie Chie" sort="Hung, Mie Chie" uniqKey="Hung M" first="Mie-Chie" last="Hung">Mie-Chie Hung</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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