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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pro-nerve Growth Factor Induces Autocrine Stimulation of Breast Cancer Cell Invasion through Tropomyosin-related Kinase A (TrkA) and Sortilin Protein<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</title>
<author><name sortKey="Demont, Yohann" sort="Demont, Yohann" uniqKey="Demont Y" first="Yohann" last="Demont">Yohann Demont</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Corbet, Cyril" sort="Corbet, Cyril" uniqKey="Corbet C" first="Cyril" last="Corbet">Cyril Corbet</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Page, Adeline" sort="Page, Adeline" uniqKey="Page A" first="Adeline" last="Page">Adeline Page</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ataman Nal, Yasemin" sort="Ataman Nal, Yasemin" uniqKey="Ataman Nal Y" first="Yasemin" last="Ataman-Önal">Yasemin Ataman-Önal</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Choquet Kastylevsky, Genevieve" sort="Choquet Kastylevsky, Genevieve" uniqKey="Choquet Kastylevsky G" first="Genevieve" last="Choquet-Kastylevsky">Genevieve Choquet-Kastylevsky</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fliniaux, Ingrid" sort="Fliniaux, Ingrid" uniqKey="Fliniaux I" first="Ingrid" last="Fliniaux">Ingrid Fliniaux</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Le Bourhis, Xuefen" sort="Le Bourhis, Xuefen" uniqKey="Le Bourhis X" first="Xuefen" last="Le Bourhis">Xuefen Le Bourhis</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Toillon, Robert Alain" sort="Toillon, Robert Alain" uniqKey="Toillon R" first="Robert-Alain" last="Toillon">Robert-Alain Toillon</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bradshaw, Ralph A" sort="Bradshaw, Ralph A" uniqKey="Bradshaw R" first="Ralph A." last="Bradshaw">Ralph A. Bradshaw</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hondermarck, Hubert" sort="Hondermarck, Hubert" uniqKey="Hondermarck H" first="Hubert" last="Hondermarck">Hubert Hondermarck</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">22128158</idno>
<idno type="pmc">3265873</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265873</idno>
<idno type="RBID">PMC:3265873</idno>
<idno type="doi">10.1074/jbc.M110.211714</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">001916</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001916</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pro-nerve Growth Factor Induces Autocrine Stimulation of Breast Cancer Cell Invasion through Tropomyosin-related Kinase A (TrkA) and Sortilin Protein<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</title>
<author><name sortKey="Demont, Yohann" sort="Demont, Yohann" uniqKey="Demont Y" first="Yohann" last="Demont">Yohann Demont</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Corbet, Cyril" sort="Corbet, Cyril" uniqKey="Corbet C" first="Cyril" last="Corbet">Cyril Corbet</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Page, Adeline" sort="Page, Adeline" uniqKey="Page A" first="Adeline" last="Page">Adeline Page</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ataman Nal, Yasemin" sort="Ataman Nal, Yasemin" uniqKey="Ataman Nal Y" first="Yasemin" last="Ataman-Önal">Yasemin Ataman-Önal</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Choquet Kastylevsky, Genevieve" sort="Choquet Kastylevsky, Genevieve" uniqKey="Choquet Kastylevsky G" first="Genevieve" last="Choquet-Kastylevsky">Genevieve Choquet-Kastylevsky</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fliniaux, Ingrid" sort="Fliniaux, Ingrid" uniqKey="Fliniaux I" first="Ingrid" last="Fliniaux">Ingrid Fliniaux</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Le Bourhis, Xuefen" sort="Le Bourhis, Xuefen" uniqKey="Le Bourhis X" first="Xuefen" last="Le Bourhis">Xuefen Le Bourhis</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Toillon, Robert Alain" sort="Toillon, Robert Alain" uniqKey="Toillon R" first="Robert-Alain" last="Toillon">Robert-Alain Toillon</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bradshaw, Ralph A" sort="Bradshaw, Ralph A" uniqKey="Bradshaw R" first="Ralph A." last="Bradshaw">Ralph A. Bradshaw</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hondermarck, Hubert" sort="Hondermarck, Hubert" uniqKey="Hondermarck H" first="Hubert" last="Hondermarck">Hubert Hondermarck</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of Biological Chemistry</title>
<idno type="ISSN">0021-9258</idno>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass></textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p>The precursor of nerve growth factor (proNGF) has been described as a biologically active polypeptide able to induce apoptosis in neuronal cells, via the neurotrophin receptor p75<sup>NTR</sup>
and the sortilin receptor. Herein, it is shown that proNGF is produced and secreted by breast cancer cells, stimulating their invasion. Using Western blotting and mass spectrometry, proNGF was detected in a panel of breast cancer cells as well as in their conditioned media. Immunohistochemical analysis indicated an overproduction of proNGF in breast tumors, when compared with benign and normal breast biopsies, and a relationship to lymph node invasion in ductal carcinomas. Interestingly, siRNA against proNGF induced a decrease of breast cancer cell invasion that was restored by the addition of non-cleavable proNGF. The activation of TrkA, Akt, and Src, but not the MAP kinases, was observed. In addition, the proNGF invasive effect was inhibited by the Trk pharmacological inhibitor K252a, a kinase-dead TrkA, and siRNA against TrkA sortilin, neurotensin, whereas siRNA against p75<sup>NTR</sup>
and the MAP kinase inhibitor PD98059 had no impact. These data reveal the existence of an autocrine loop stimulated by proNGF and mediated by TrkA and sortilin, with the activation of Akt and Src, for the stimulation of breast cancer cell invasion.</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">J Biol Chem</journal-id>
<journal-id journal-id-type="hwp">jbc</journal-id>
<journal-id journal-id-type="pmc">jbc</journal-id>
<journal-id journal-id-type="publisher-id">JBC</journal-id>
<journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title>
</journal-title-group>
<issn pub-type="ppub">0021-9258</issn>
<issn pub-type="epub">1083-351X</issn>
<publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name>
<publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22128158</article-id>
<article-id pub-id-type="pmc">3265873</article-id>
<article-id pub-id-type="publisher-id">M110.211714</article-id>
<article-id pub-id-type="doi">10.1074/jbc.M110.211714</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Molecular Bases of Disease</subject>
</subj-group>
</article-categories>
<title-group><article-title>Pro-nerve Growth Factor Induces Autocrine Stimulation of Breast Cancer Cell Invasion through Tropomyosin-related Kinase A (TrkA) and Sortilin Protein<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</article-title>
<alt-title alt-title-type="short">Autocrine proNGF in Breast Cancer</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Demont</surname>
<given-names>Yohann</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="author-notes" rid="FN3"><sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="FN4"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Corbet</surname>
<given-names>Cyril</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="author-notes" rid="FN3"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Page</surname>
<given-names>Adeline</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>§</sup>
</xref>
<xref ref-type="author-notes" rid="FN5"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ataman-Önal</surname>
<given-names>Yasemin</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Choquet-Kastylevsky</surname>
<given-names>Genevieve</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>¶</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fliniaux</surname>
<given-names>Ingrid</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Le Bourhis</surname>
<given-names>Xuefen</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Toillon</surname>
<given-names>Robert-Alain</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bradshaw</surname>
<given-names>Ralph A.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>‖</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hondermarck</surname>
<given-names>Hubert</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>‡</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>4</sup>
</xref>
</contrib>
<aff id="aff1">From<label>‡</label>
INSERM U908 Growth Factor Signaling in Breast Cancer and</aff>
<aff id="aff2">the<label>§</label>
Mass Spectrometry Facility, IFR-147, University of Lille, Villeneuve d'Ascq 59655, France,</aff>
<aff id="aff3">the<label>¶</label>
Department for Biomarker Research and Validation, BioMérieux, F-69280 Marcy l'Etoile, France, and</aff>
<aff id="aff4">the<label>‖</label>
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158</aff>
</contrib-group>
<author-notes><corresp id="cor1"><label>4</label>
To whom correspondence should be addressed: <addr-line>School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan NSW 2308, Australia.</addr-line>
E-mail: <email>hubert.hondermarck@newcastle.edu.au</email>
.</corresp>
<fn fn-type="equal" id="FN3"><label>1</label>
<p>Both authors contributed equally to this work.</p>
</fn>
<fn fn-type="other" id="FN4"><label>2</label>
<p>Recipient of a fellowship from the “Association pour la Recherche sur le Cancer.”</p>
</fn>
<fn fn-type="present-address" id="FN5"><label>3</label>
<p>Present address: Laboratory of Mass Spectrometry, Institute of Genetic and Molecular and Cellular Biology, 67404 Illkirch CEDEX, France.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>13</day>
<month>1</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>29</day>
<month>11</month>
<year>2011</year>
</pub-date>
<volume>287</volume>
<issue>3</issue>
<fpage>1923</fpage>
<lpage>1931</lpage>
<history><date date-type="received"><day>12</day>
<month>12</month>
<year>2010</year>
</date>
<date date-type="rev-recd"><day>25</day>
<month>11</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc00312001923.pdf"></self-uri>
<abstract><p>The precursor of nerve growth factor (proNGF) has been described as a biologically active polypeptide able to induce apoptosis in neuronal cells, via the neurotrophin receptor p75<sup>NTR</sup>
and the sortilin receptor. Herein, it is shown that proNGF is produced and secreted by breast cancer cells, stimulating their invasion. Using Western blotting and mass spectrometry, proNGF was detected in a panel of breast cancer cells as well as in their conditioned media. Immunohistochemical analysis indicated an overproduction of proNGF in breast tumors, when compared with benign and normal breast biopsies, and a relationship to lymph node invasion in ductal carcinomas. Interestingly, siRNA against proNGF induced a decrease of breast cancer cell invasion that was restored by the addition of non-cleavable proNGF. The activation of TrkA, Akt, and Src, but not the MAP kinases, was observed. In addition, the proNGF invasive effect was inhibited by the Trk pharmacological inhibitor K252a, a kinase-dead TrkA, and siRNA against TrkA sortilin, neurotensin, whereas siRNA against p75<sup>NTR</sup>
and the MAP kinase inhibitor PD98059 had no impact. These data reveal the existence of an autocrine loop stimulated by proNGF and mediated by TrkA and sortilin, with the activation of Akt and Src, for the stimulation of breast cancer cell invasion.</p>
</abstract>
<kwd-group><kwd>Breast Cancer</kwd>
<kwd>Cellular Regulation</kwd>
<kwd>Growth Factors</kwd>
<kwd>Neurotrophins</kwd>
<kwd>Signal Transduction</kwd>
<kwd>TrkA Receptor</kwd>
<kwd>p75NTR</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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