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<title xml:lang="en">Overexpression of forkhead Box C2 promotes tumor metastasis and indicates poor prognosis in colon cancer via regulating epithelial-mesenchymal transition</title>
<author>
<name sortKey="Li, Qingguo" sort="Li, Qingguo" uniqKey="Li Q" first="Qingguo" last="Li">Qingguo Li</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wu, Jitao" sort="Wu, Jitao" uniqKey="Wu J" first="Jitao" last="Wu">Jitao Wu</name>
<affiliation>
<nlm:aff id="au3">
<institution>Department of Urology, Yantai Yuhuangding Hospital</institution>
<addr-line>Yantai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au4">
<institution>Departments of Pathology, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Xu, Ye" sort="Xu, Ye" uniqKey="Xu Y" first="Ye" last="Xu">Ye Xu</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Zhuo, Changhua" sort="Zhuo, Changhua" uniqKey="Zhuo C" first="Changhua" last="Zhuo">Changhua Zhuo</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wang, Yuwei" sort="Wang, Yuwei" uniqKey="Wang Y" first="Yuwei" last="Wang">Yuwei Wang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Li, Dawei" sort="Li, Dawei" uniqKey="Li D" first="Dawei" last="Li">Dawei Li</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cai, Sanjun" sort="Cai, Sanjun" uniqKey="Cai S" first="Sanjun" last="Cai">Sanjun Cai</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
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<idno type="RBID">PMC:4529621</idno>
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<title xml:lang="en" level="a" type="main">Overexpression of forkhead Box C2 promotes tumor metastasis and indicates poor prognosis in colon cancer via regulating epithelial-mesenchymal transition</title>
<author>
<name sortKey="Li, Qingguo" sort="Li, Qingguo" uniqKey="Li Q" first="Qingguo" last="Li">Qingguo Li</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wu, Jitao" sort="Wu, Jitao" uniqKey="Wu J" first="Jitao" last="Wu">Jitao Wu</name>
<affiliation>
<nlm:aff id="au3">
<institution>Department of Urology, Yantai Yuhuangding Hospital</institution>
<addr-line>Yantai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au4">
<institution>Departments of Pathology, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Xu, Ye" sort="Xu, Ye" uniqKey="Xu Y" first="Ye" last="Xu">Ye Xu</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Zhuo, Changhua" sort="Zhuo, Changhua" uniqKey="Zhuo C" first="Changhua" last="Zhuo">Changhua Zhuo</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wang, Yuwei" sort="Wang, Yuwei" uniqKey="Wang Y" first="Yuwei" last="Wang">Yuwei Wang</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Li, Dawei" sort="Li, Dawei" uniqKey="Li D" first="Dawei" last="Li">Dawei Li</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cai, Sanjun" sort="Cai, Sanjun" uniqKey="Cai S" first="Sanjun" last="Cai">Sanjun Cai</name>
<affiliation>
<nlm:aff id="au1">
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="au2">
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">American Journal of Cancer Research</title>
<idno type="eISSN">2156-6976</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
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</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Forkhead box protein C2 (FOXC2) plays a vital role in carcinogenesis; however, its significance and prognostic value in colon cancer remain unclear. In this study, FOXC2 expression was analyzed in a tissue microarray (TMA) containing 185 samples of primary colon cancer tumor samples and in human colon cancer cell lines. The effect of FOXC2 on cell proliferation, tumorigenesis, and metastasis was examined
<italic>in vitro</italic>
and
<italic>in vivo</italic>
. FOXC2 was overexpressed in human colon cancer cells and tissues, and correlated with colon cancer progression and patient survival. Functional study demonstrated that FOXC2 promoted cell growth, cell migration, and tumor formation in nude mice, whereas knockdown of FOXC2 by short hairpin RNA (shRNAs) significantly suppressed cell growth, cell migration and tumor formation. Further study found that FOXC2 enhanced AKT activity with subsequent GSK-3β phosphorylation and Snail stabilization, and then induced epithelial-mesenchymal transition (EMT) and promoted tumor invasion and metastasis. Collectively, FOXC2 promotes colon cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colon cancer.</p>
</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">Am J Cancer Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Am J Cancer Res</journal-id>
<journal-id journal-id-type="publisher-id">ajcr</journal-id>
<journal-title-group>
<journal-title>American Journal of Cancer Research</journal-title>
</journal-title-group>
<issn pub-type="epub">2156-6976</issn>
<publisher>
<publisher-name>e-Century Publishing Corporation</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26269761</article-id>
<article-id pub-id-type="pmc">4529621</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Overexpression of forkhead Box C2 promotes tumor metastasis and indicates poor prognosis in colon cancer via regulating epithelial-mesenchymal transition</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Qingguo</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wu</surname>
<given-names>Jitao</given-names>
</name>
<xref ref-type="aff" rid="au3">3</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wei</surname>
<given-names>Ping</given-names>
</name>
<xref ref-type="aff" rid="au2">2</xref>
<xref ref-type="aff" rid="au4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Xu</surname>
<given-names>Ye</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhuo</surname>
<given-names>Changhua</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Yuwei</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Dawei</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cai</surname>
<given-names>Sanjun</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<aff id="au1">
<label>1</label>
<institution>Departments of Colorectal Surgery, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</aff>
<aff id="au2">
<label>2</label>
<institution>Department of Oncology, Shanghai Medical College, Fudan University</institution>
<addr-line>Shanghai, China</addr-line>
</aff>
<aff id="au3">
<label>3</label>
<institution>Department of Urology, Yantai Yuhuangding Hospital</institution>
<addr-line>Yantai, China</addr-line>
</aff>
<aff id="au4">
<label>4</label>
<institution>Departments of Pathology, Fudan University Shanghai Cancer Center</institution>
<addr-line>Shanghai, China</addr-line>
</aff>
</contrib-group>
<author-notes>
<corresp>
<bold>Address correspondence to:</bold>
Sanjun Cai, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. E-mail:
<email>caisanjun_sh@163.com</email>
; Dawei Li, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. E-mail:
<email>davidleehero@126.com</email>
</corresp>
<fn id="fn1">
<label>*</label>
<p>Equal contributors.</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>15</day>
<month>5</month>
<year>2015</year>
</pub-date>
<volume>5</volume>
<issue>6</issue>
<fpage>2022</fpage>
<lpage>2034</lpage>
<history>
<date date-type="received">
<day>19</day>
<month>3</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>4</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>AJCR Copyright © 2015</copyright-statement>
<copyright-year>2015</copyright-year>
</permissions>
<abstract>
<p>Forkhead box protein C2 (FOXC2) plays a vital role in carcinogenesis; however, its significance and prognostic value in colon cancer remain unclear. In this study, FOXC2 expression was analyzed in a tissue microarray (TMA) containing 185 samples of primary colon cancer tumor samples and in human colon cancer cell lines. The effect of FOXC2 on cell proliferation, tumorigenesis, and metastasis was examined
<italic>in vitro</italic>
and
<italic>in vivo</italic>
. FOXC2 was overexpressed in human colon cancer cells and tissues, and correlated with colon cancer progression and patient survival. Functional study demonstrated that FOXC2 promoted cell growth, cell migration, and tumor formation in nude mice, whereas knockdown of FOXC2 by short hairpin RNA (shRNAs) significantly suppressed cell growth, cell migration and tumor formation. Further study found that FOXC2 enhanced AKT activity with subsequent GSK-3β phosphorylation and Snail stabilization, and then induced epithelial-mesenchymal transition (EMT) and promoted tumor invasion and metastasis. Collectively, FOXC2 promotes colon cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colon cancer.</p>
</abstract>
<kwd-group>
<kwd>FOXC2</kwd>
<kwd>colon cancer</kwd>
<kwd>metastasis</kwd>
<kwd>EMT</kwd>
<kwd>prognostic factor</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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