Forkhead box K1 regulates the malignant behavior of gastric cancer by inhibiting autophagy
Identifieur interne : 000141 ( Pmc/Checkpoint ); précédent : 000140; suivant : 000142Forkhead box K1 regulates the malignant behavior of gastric cancer by inhibiting autophagy
Auteurs : Yixuan Wang [République populaire de Chine] ; Wensheng Qiu [République populaire de Chine] ; Ning Liu [République populaire de Chine] ; Libin Sun [République populaire de Chine] ; Zhao Liu [République populaire de Chine] ; Shasha Wang [République populaire de Chine] ; Peng Wang ; Shihai Liu [République populaire de Chine] ; Jing Lv [République populaire de Chine]Source :
- Annals of Translational Medicine [ 2305-5839 ] ; 2020.
Abstract
Forkhead box K1 (FOXK1) is a transcription factor that contributes to cancer development, but it is unclear how FOXK1 regulates the proliferation and migration of gastric cancer (GC) cells. The purpose of this study was to investigate the clinical significance, biological function, and molecular mechanisms of FOXK1 in GC.
We conducted bioinformatics assays and western blotting to assess FOXK1 expression. Then, we performed immunohistochemistry (IHC) with tissue microarrays (TMAs) to assess FOXK1 expression in order to identify an association between FOXK1 expression levels and clinical parameters. We used 5-ethynyl-2’-deoxyuridine (EdU), wound healing and Transwell assays to determine whether FOXK1 promotes malignant behaviors in GC. Furthermore, immunofluorescence staining, transmission electron microscopy and western blotting were used to verify an association between FOXK1 and autophagy.
We observed high levels of FOXK1 expression in GC tissues, which were associated with the degree of malignancy in GC. FOXK1 promotes the malignant behavior of GC by regulating autophagy via activation of the class I phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and inhibition of the expression of class III PI3K.
These findings provide a new target for the comprehensive treatment of GC by highlighting the relationship between FOXK1 and malignant behaviors in GC.
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DOI: 10.21037/atm.2019.12.123
PubMed: 32175400
PubMed Central: 7049027
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xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Ning" sort="Liu, Ning" uniqKey="Liu N" first="Ning" last="Liu">Ning Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Libin" sort="Sun, Libin" uniqKey="Sun L" first="Libin" last="Sun">Libin Sun</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Zhao" sort="Liu, Zhao" uniqKey="Liu Z" first="Zhao" last="Liu">Zhao Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Shasha" sort="Wang, Shasha" uniqKey="Wang S" first="Shasha" last="Wang">Shasha Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Peng" sort="Wang, Peng" uniqKey="Wang P" first="Peng" last="Wang">Peng Wang</name><affiliation><nlm:aff id="aff2">Department of Oncology, Weifang Yidu Central Hospital, Qingzhou<addr-line>262500,<country>China</country></addr-line>;</nlm:aff></affiliation></author><author><name sortKey="Liu, Shihai" sort="Liu, Shihai" uniqKey="Liu S" first="Shihai" last="Liu">Shihai Liu</name><affiliation wicri:level="1"><nlm:aff id="aff3">Central Laboratory,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lv, Jing" sort="Lv, Jing" uniqKey="Lv J" first="Jing" last="Lv">Jing Lv</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32175400</idno><idno type="pmc">7049027</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049027</idno><idno type="RBID">PMC:7049027</idno><idno type="doi">10.21037/atm.2019.12.123</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000359</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000359</idno><idno type="wicri:Area/Pmc/Curation">000359</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000359</idno><idno type="wicri:Area/Pmc/Checkpoint">000141</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000141</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Forkhead box K1 regulates the malignant behavior of gastric cancer by inhibiting autophagy</title><author><name sortKey="Wang, Yixuan" sort="Wang, Yixuan" uniqKey="Wang Y" first="Yixuan" last="Wang">Yixuan Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qiu, Wensheng" sort="Qiu, Wensheng" uniqKey="Qiu W" first="Wensheng" last="Qiu">Wensheng Qiu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Ning" sort="Liu, Ning" uniqKey="Liu N" first="Ning" last="Liu">Ning Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sun, Libin" sort="Sun, Libin" uniqKey="Sun L" first="Libin" last="Sun">Libin Sun</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Zhao" sort="Liu, Zhao" uniqKey="Liu Z" first="Zhao" last="Liu">Zhao Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Shasha" sort="Wang, Shasha" uniqKey="Wang S" first="Shasha" last="Wang">Shasha Wang</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Peng" sort="Wang, Peng" uniqKey="Wang P" first="Peng" last="Wang">Peng Wang</name><affiliation><nlm:aff id="aff2">Department of Oncology, Weifang Yidu Central Hospital, Qingzhou<addr-line>262500,<country>China</country></addr-line>;</nlm:aff></affiliation></author><author><name sortKey="Liu, Shihai" sort="Liu, Shihai" uniqKey="Liu S" first="Shihai" last="Liu">Shihai Liu</name><affiliation wicri:level="1"><nlm:aff id="aff3">Central Laboratory,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lv, Jing" sort="Lv, Jing" uniqKey="Lv J" first="Jing" last="Lv">Jing Lv</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Annals of Translational Medicine</title><idno type="ISSN">2305-5839</idno><idno type="eISSN">2305-5847</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Forkhead box K1 (FOXK1) is a transcription factor that contributes to cancer development, but it is unclear how FOXK1 regulates the proliferation and migration of gastric cancer (GC) cells. The purpose of this study was to investigate the clinical significance, biological function, and molecular mechanisms of FOXK1 in GC.</p></sec><sec><title>Methods</title><p>We conducted bioinformatics assays and western blotting to assess FOXK1 expression. Then, we performed immunohistochemistry (IHC) with tissue microarrays (TMAs) to assess FOXK1 expression in order to identify an association between FOXK1 expression levels and clinical parameters. We used 5-ethynyl-2’-deoxyuridine (EdU), wound healing and Transwell assays to determine whether FOXK1 promotes malignant behaviors in GC. Furthermore, immunofluorescence staining, transmission electron microscopy and western blotting were used to verify an association between FOXK1 and autophagy.</p></sec><sec><title>Results</title><p>We observed high levels of FOXK1 expression in GC tissues, which were associated with the degree of malignancy in GC. FOXK1 promotes the malignant behavior of GC by regulating autophagy via activation of the class I phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and inhibition of the expression of class III PI3K.</p></sec><sec><title>Conclusions</title><p>These findings provide a new target for the comprehensive treatment of GC by highlighting the relationship between FOXK1 and malignant behaviors in GC.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Ann Transl Med</journal-id><journal-id journal-id-type="iso-abbrev">Ann Transl Med</journal-id><journal-id journal-id-type="publisher-id">ATM</journal-id><journal-title-group><journal-title>Annals of Translational Medicine</journal-title></journal-title-group><issn pub-type="ppub">2305-5839</issn><issn pub-type="epub">2305-5847</issn><publisher><publisher-name>AME Publishing Company</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32175400</article-id><article-id pub-id-type="pmc">7049027</article-id><article-id pub-id-type="publisher-id">atm-08-04-107</article-id><article-id pub-id-type="doi">10.21037/atm.2019.12.123</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Forkhead box K1 regulates the malignant behavior of gastric cancer by inhibiting autophagy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yixuan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="afn2"><sup>#</sup></xref></contrib><contrib contrib-type="author"><name><surname>Qiu</surname><given-names>Wensheng</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="afn2"><sup>#</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Ning</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Libin</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Zhao</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Shasha</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Peng</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Liu</surname><given-names>Shihai</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Lv</surname><given-names>Jing</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><aff id="aff1"><label>1</label>Department of Oncology,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country>;</aff><aff id="aff2"><label>2</label>Department of Oncology, Weifang Yidu Central Hospital, Qingzhou<addr-line>262500,<country>China</country></addr-line>;</aff><aff id="aff3"><label>3</label>Central Laboratory,<institution>the Affiliated Hospital of Qingdao University</institution>,<addr-line>Qingdao 266071</addr-line>,<country>China</country></aff></contrib-group><author-notes><fn id="afn1"><p><italic>Contributions:</italic> (I) Conception and design: Y Wang; (II) Administrative support: W Qiu, S Liu, J Lv; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.</p></fn><fn id="afn2" fn-type="equal"><label>#</label><p>These authors contributed equally to this work.</p></fn><corresp id="cor1"><italic>Correspondence to:</italic> Dr. Jing Lv. Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266071, China. Email: <email xlink:href="lvjing8291@126.com">lvjing8291@126.com</email>; Dr. Shihai Liu. Central Laboratory, the Affiliated Hospital of Qingdao University, Qingdao 266071, China. Email: <email xlink:href="shliumed@126.com">shliumed@126.com</email>.</corresp><fn fn-type="COI-statement"><p><italic>Conflicts of Interest:</italic> The authors declare no conflicts of interest.</p></fn></author-notes><pub-date pub-type="epub-ppub"><month>2</month><year>2020</year></pub-date><pmc-comment>Fake ppub date generated by PMC from publisher
pub-date/@pub-type='epub-ppub' </pmc-comment>
<pub-date pub-type="ppub"><month>2</month><year>2020</year></pub-date><volume>8</volume><issue>4</issue><elocation-id>107</elocation-id><history><date date-type="received"><day>15</day><month>8</month><year>2019</year></date><date date-type="accepted"><day>29</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>2020 Annals of Translational Medicine. All rights reserved.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>Annals of Translational Medicine.</copyright-holder></permissions><abstract><sec><title>Background</title><p>Forkhead box K1 (FOXK1) is a transcription factor that contributes to cancer development, but it is unclear how FOXK1 regulates the proliferation and migration of gastric cancer (GC) cells. The purpose of this study was to investigate the clinical significance, biological function, and molecular mechanisms of FOXK1 in GC.</p></sec><sec><title>Methods</title><p>We conducted bioinformatics assays and western blotting to assess FOXK1 expression. Then, we performed immunohistochemistry (IHC) with tissue microarrays (TMAs) to assess FOXK1 expression in order to identify an association between FOXK1 expression levels and clinical parameters. We used 5-ethynyl-2’-deoxyuridine (EdU), wound healing and Transwell assays to determine whether FOXK1 promotes malignant behaviors in GC. Furthermore, immunofluorescence staining, transmission electron microscopy and western blotting were used to verify an association between FOXK1 and autophagy.</p></sec><sec><title>Results</title><p>We observed high levels of FOXK1 expression in GC tissues, which were associated with the degree of malignancy in GC. FOXK1 promotes the malignant behavior of GC by regulating autophagy via activation of the class I phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and inhibition of the expression of class III PI3K.</p></sec><sec><title>Conclusions</title><p>These findings provide a new target for the comprehensive treatment of GC by highlighting the relationship between FOXK1 and malignant behaviors in GC.</p></sec></abstract><kwd-group kwd-group-type="author"><title>Keywords: </title><kwd>Forkhead box K1 (FOXK1)</kwd><kwd>autophagy</kwd><kwd>gastric cancer</kwd><kwd>3-methyladenine (3-MA)</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Wang, Peng" sort="Wang, Peng" uniqKey="Wang P" first="Peng" last="Wang">Peng Wang</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Yixuan" sort="Wang, Yixuan" uniqKey="Wang Y" first="Yixuan" last="Wang">Yixuan Wang</name></noRegion><name sortKey="Liu, Ning" sort="Liu, Ning" uniqKey="Liu N" first="Ning" last="Liu">Ning Liu</name><name sortKey="Liu, Shihai" sort="Liu, Shihai" uniqKey="Liu S" first="Shihai" last="Liu">Shihai Liu</name><name sortKey="Liu, Zhao" sort="Liu, Zhao" uniqKey="Liu Z" first="Zhao" last="Liu">Zhao Liu</name><name sortKey="Lv, Jing" sort="Lv, Jing" uniqKey="Lv J" first="Jing" last="Lv">Jing Lv</name><name sortKey="Qiu, Wensheng" sort="Qiu, Wensheng" uniqKey="Qiu W" first="Wensheng" last="Qiu">Wensheng Qiu</name><name sortKey="Sun, Libin" sort="Sun, Libin" uniqKey="Sun L" first="Libin" last="Sun">Libin Sun</name><name sortKey="Wang, Shasha" sort="Wang, Shasha" uniqKey="Wang S" first="Shasha" last="Wang">Shasha Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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