Concise Review: Neutral Endopeptidase (CD10): A Multifaceted Environment Actor in Stem Cells, Physiological Mechanisms, and Cancer | Stem Cells

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CD10 is a remarkable member of the major class of widely expressed cell surface proteins, endopeptidases. First identified in leukemia as a tumor","pageStart":"389","pageEnd":"396","siteName":"OUP Academic","thumbnailURL":"https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/stmcls/29/3/10.1002_stem.592/3/m_stmcls_29_3_389_nfig001.jpeg?Expires=1794539976&Signature=R0tdSKg87Rw1CDT73DE1acpoa7AjtF3Y3HlNgSRBZCyqJ~tGcHrYgRClw7Jnx4t6ODjJlyxUN9jW96F0eXKElaN9bDdB8zBMtNd~JPsuUTIIBDxzQSt7mnkIy1odtwOC7i39OEi-4ruL9M19fCd~dm1SVLwjukYE-P3yuAUL716zItzidsFS1lPBmG7AEfQyWarR1i1sr8QOyIpzudAof-O4uBuWP8U1mS4b4aUd82Nx9Isgpemilde7w6bB88xtp95KZCJ06utvcqkBxHX4UUu4aAMl001flohWsEpVk7nQP8wEDIoPsQ9I~ji9LN32TtpGMZUZSC-8IGdyjpIFzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA","headline":"Concise Review: Neutral Endopeptidase (CD10): A Multifaceted Environment Actor in Stem Cells, Physiological Mechanisms, and Cancer","image":"https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/stmcls/29/3/10.1002_stem.592/3/m_stmcls_29_3_389_nfig001.jpeg?Expires=1794539976&Signature=R0tdSKg87Rw1CDT73DE1acpoa7AjtF3Y3HlNgSRBZCyqJ~tGcHrYgRClw7Jnx4t6ODjJlyxUN9jW96F0eXKElaN9bDdB8zBMtNd~JPsuUTIIBDxzQSt7mnkIy1odtwOC7i39OEi-4ruL9M19fCd~dm1SVLwjukYE-P3yuAUL716zItzidsFS1lPBmG7AEfQyWarR1i1sr8QOyIpzudAof-O4uBuWP8U1mS4b4aUd82Nx9Isgpemilde7w6bB88xtp95KZCJ06utvcqkBxHX4UUu4aAMl001flohWsEpVk7nQP8wEDIoPsQ9I~ji9LN32TtpGMZUZSC-8IGdyjpIFzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA","image:alt":"CD10 structure and function. (A): Characterization of CD10 gene containing two 5′ exon splicing regions, exon 1 and exon 2a/b and a common exon 3 that contains the translation initiation codon. Three types of CD10 transcripts result from the alternative splicing of these specific 5′ untranslated regions, the type 1 transcript, where exon 1 splices directly into exon 3; the type 2a transcript, which uses an internal 5′ splicing site in exon 2; and the type 2b transcript, which uses the second 5′ splicing site (adapted from [6]). (B): Schematic representation of the mammalian primary sequences of CD10 protein including a short NH2-terminal cytoplasmic domain of 27 residues named ICD that induces signaling, a short sequence of 22 hydrophobic residues that forms a single TMD and a long ECD of 700 residues that contains the active zincin motif (HExxH H histidin and E: glutamic acid) represented by a black rectangle. Cystein residues are indicated by (•), Histidin H711, which is responsible for stabilization of the transition state by (▪) and the catalytic glutamate E646 by (▴). (C): Ribbon plot of CD10 with the volume of the spherical active site cavity represented in yellow. The cavity has a diameter of 20Å [12]. (D): CD10 signaling pathways. CD10 associates with p85, a PI3K subunit, and Lyn kinase indirectly prevents FAK activation by PI3K. Simultaneously, the association between CD10 and the tumor suppressor PTEN simultaneously leads to decreased PIP3 phosphorylation, which activates the Akt pathway [7]. CD10 catalytically inactivates a variety of peptides like bombesin in prostate cancer cells, which induces FAK or Rho signaling by their fixation onto G-coupled protein receptor [8]. CD10 also cleaves growth factors such as fibroblast growth factor 2 (FGF2), which induces Akt signaling in favor of endothelial cell growth and angiogenesis [9]. Abbreviations: BL, basal lame; ECD, extracellular domain; FAK, focal adhesion kinase; FGF2, fibroblast growth factor 2; GF, growth factor; GFR, growth factor receptor; GPCR, G protein-coupled receptor; GPI, glycosylphosphatidylinositol; GSK3, glycogen synthase kinase 3; ICD, intracellular domain; ILK, integrin-linked kinase; MDM2, murine double minute 2; P85, PI3K subunit (85 KDa); PI3K, phosphatidylinositol 3-kinases; PIP3, phosphatidylinositol 3,4,5-trisphosphate; PTEN, phosphatase and TENsin homolog; ROCK, Rho-associated protein kinase; TMD, transmembrane helix domain."} </script> <meta property="og:site_name" content="OUP Academic" /> <meta property="og:title" content="Concise Review: Neutral Endopeptidase (CD10): A Multifaceted Environment Actor in Stem Cells, Physiological Mechanisms, and Cancer" /> <meta property="og:description" content="Abstract. CD10 is a remarkable member of the major class of widely expressed cell surface proteins, endopeptidases. First identified in leukemia as a tumor" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://dx.doi.org/10.1002/stem.592" /> <meta property="og:updated_time" content="" /> <meta property="og:image" content="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/stmcls/29/3/10.1002_stem.592/3/m_stmcls_29_3_389_nfig001.jpeg?Expires=1794539976&Signature=R0tdSKg87Rw1CDT73DE1acpoa7AjtF3Y3HlNgSRBZCyqJ~tGcHrYgRClw7Jnx4t6ODjJlyxUN9jW96F0eXKElaN9bDdB8zBMtNd~JPsuUTIIBDxzQSt7mnkIy1odtwOC7i39OEi-4ruL9M19fCd~dm1SVLwjukYE-P3yuAUL716zItzidsFS1lPBmG7AEfQyWarR1i1sr8QOyIpzudAof-O4uBuWP8U1mS4b4aUd82Nx9Isgpemilde7w6bB88xtp95KZCJ06utvcqkBxHX4UUu4aAMl001flohWsEpVk7nQP8wEDIoPsQ9I~ji9LN32TtpGMZUZSC-8IGdyjpIFzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:image:url" content="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/stmcls/29/3/10.1002_stem.592/3/m_stmcls_29_3_389_nfig001.jpeg?Expires=1794539976&Signature=R0tdSKg87Rw1CDT73DE1acpoa7AjtF3Y3HlNgSRBZCyqJ~tGcHrYgRClw7Jnx4t6ODjJlyxUN9jW96F0eXKElaN9bDdB8zBMtNd~JPsuUTIIBDxzQSt7mnkIy1odtwOC7i39OEi-4ruL9M19fCd~dm1SVLwjukYE-P3yuAUL716zItzidsFS1lPBmG7AEfQyWarR1i1sr8QOyIpzudAof-O4uBuWP8U1mS4b4aUd82Nx9Isgpemilde7w6bB88xtp95KZCJ06utvcqkBxHX4UUu4aAMl001flohWsEpVk7nQP8wEDIoPsQ9I~ji9LN32TtpGMZUZSC-8IGdyjpIFzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:image:secure_url" content="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/stmcls/29/3/10.1002_stem.592/3/m_stmcls_29_3_389_nfig001.jpeg?Expires=1794539976&Signature=R0tdSKg87Rw1CDT73DE1acpoa7AjtF3Y3HlNgSRBZCyqJ~tGcHrYgRClw7Jnx4t6ODjJlyxUN9jW96F0eXKElaN9bDdB8zBMtNd~JPsuUTIIBDxzQSt7mnkIy1odtwOC7i39OEi-4ruL9M19fCd~dm1SVLwjukYE-P3yuAUL716zItzidsFS1lPBmG7AEfQyWarR1i1sr8QOyIpzudAof-O4uBuWP8U1mS4b4aUd82Nx9Isgpemilde7w6bB88xtp95KZCJ06utvcqkBxHX4UUu4aAMl001flohWsEpVk7nQP8wEDIoPsQ9I~ji9LN32TtpGMZUZSC-8IGdyjpIFzw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" /> <meta property="og:image:alt" content="CD10 structure and function. (A): Characterization of CD10 gene containing two 5′ exon splicing regions, exon 1 and exon 2a/b and a common exon 3 that contains the translation initiation codon. Three types of CD10 transcripts result from the alternative splicing of these specific 5′ untranslated regions, the type 1 transcript, where exon 1 splices directly into exon 3; the type 2a transcript, which uses an internal 5′ splicing site in exon 2; and the type 2b transcript, which uses the second 5′ splicing site (adapted from [6]). (B): Schematic representation of the mammalian primary sequences of CD10 protein including a short NH2-terminal cytoplasmic domain of 27 residues named ICD that induces signaling, a short sequence of 22 hydrophobic residues that forms a single TMD and a long ECD of 700 residues that contains the active zincin motif (HExxH H histidin and E: glutamic acid) represented by a black rectangle. Cystein residues are indicated by (•), Histidin H711, which is responsible for stabilization of the transition state by (▪) and the catalytic glutamate E646 by (▴). (C): Ribbon plot of CD10 with the volume of the spherical active site cavity represented in yellow. The cavity has a diameter of 20Å [12]. (D): CD10 signaling pathways. CD10 associates with p85, a PI3K subunit, and Lyn kinase indirectly prevents FAK activation by PI3K. Simultaneously, the association between CD10 and the tumor suppressor PTEN simultaneously leads to decreased PIP3 phosphorylation, which activates the Akt pathway [7]. CD10 catalytically inactivates a variety of peptides like bombesin in prostate cancer cells, which induces FAK or Rho signaling by their fixation onto G-coupled protein receptor [8]. CD10 also cleaves growth factors such as fibroblast growth factor 2 (FGF2), which induces Akt signaling in favor of endothelial cell growth and angiogenesis [9]. Abbreviations: BL, basal lame; ECD, extracellular domain; FAK, focal adhesion kinase; FGF2, fibroblast growth factor 2; GF, growth factor; GFR, growth factor receptor; GPCR, G protein-coupled receptor; GPI, glycosylphosphatidylinositol; GSK3, glycogen synthase kinase 3; ICD, intracellular domain; ILK, integrin-linked kinase; MDM2, murine double minute 2; P85, PI3K subunit (85 KDa); PI3K, phosphatidylinositol 3-kinases; PIP3, phosphatidylinositol 3,4,5-trisphosphate; PTEN, phosphatase and TENsin homolog; ROCK, Rho-associated protein kinase; TMD, transmembrane helix domain." /> <meta name="twitter:card" content="summary_large_image" /> <meta name="citation_author" content="Maguer-Satta, Veronique" /><meta name="citation_author_institution" content="Université de Lyon, Lyon, F-69007, France" /><meta name="citation_author_institution" content="Inserm, U590, Centre Léon Bérard, Lyon, F-69008, Lyon, France" /><meta name="citation_author_institution" content="IFR62, Lyon, F-69008, France" /><meta name="citation_author" content="Besançon, Roger" /><meta name="citation_author_institution" content="Université de Lyon, Lyon, F-69007, France" /><meta name="citation_author_institution" content="Inserm, U590, Centre Léon Bérard, Lyon, F-69008, Lyon, France" /><meta name="citation_author_institution" content="IFR62, Lyon, F-69008, France" /><meta name="citation_author_institution" content="Université de Lyon 1, ISPB, F-69008, France" /><meta name="citation_author" content="Bachelard-Cascales, Elodie" /><meta name="citation_author_institution" content="Université de Lyon, Lyon, F-69007, France" /><meta name="citation_author_institution" content="Inserm, U590, Centre Léon Bérard, Lyon, F-69008, Lyon, France" /><meta name="citation_author_institution" content="IFR62, Lyon, F-69008, France" /><meta name="citation_title" content="Concise Review: Neutral Endopeptidase (CD10): A Multifaceted Environment Actor in Stem Cells, Physiological Mechanisms, and Cancer" /><meta name="citation_firstpage" content="389" /><meta name="citation_lastpage" content="396" /><meta name="citation_doi" content="10.1002/stem.592" /><meta name="citation_journal_title" content="Stem Cells" /><meta name="citation_journal_abbrev" content="Stem Cells" /><meta name="citation_volume" content="29" /><meta name="citation_issue" content="3" /><meta name="citation_publication_date" content="2011/03/01" /><meta name="citation_issn" content="1066-5099" /><meta name="citation_publisher" content="Oxford Academic" /><meta name="citation_reference" content="citation_title=Regulation of matrix biology by matrix metalloproteinases; 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class="journal-info__format-label">Journal Article</span> </div> <div class="widget-items"> <div class="title-wrap"> <h1 class="wi-article-title article-title-main accessible-content-title at-articleTitle"> Concise Review: Neutral Endopeptidase (CD10): A Multifaceted Environment Actor in Stem Cells, Physiological Mechanisms, and Cancer <i class='' title='' ></i> </h1> <a href="#no-access-message" class="get-access get-access-jumplink at-get-access-jumplink js-no-access-jumplink"> <span class="get-access-text">Get access</span> <img class='get-access-icon' src='/UI/app/svg/chevron-right-white.svg' alt='Arrow' aria-hidden='true'> </a> </div> <div class="wi-authors at-ArticleAuthors"> <div class="al-authors-list"> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Veronique Maguer-Satta, PhD, CR1 CNRS</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Veronique Maguer-Satta, PhD, CR1 CNRS <span class="info-card-footnote"><span class="xrefLink" id="jumplink-cor1"></span><a href="javascript:;" reveal-id="cor1" data-open="cor1" class="link link-ref link-reveal xref-default"></a></span> <span class="info-card-footnote"><span class="xrefLink" id="jumplink-fn4"></span><a href="javascript:;" reveal-id="fn4" data-open="fn4" class="link link-ref link-reveal xref-default"></a></span> </div> </div> <div class="info-card-affilitation"> <div class="aff"><div class="institution">Université de Lyon</div>, Lyon, F-69007, <div class="country">France</div></div><div class="aff"><div class="institution">Inserm, U590, Centre Léon Bérard</div>, Lyon, F-69008, Lyon, <div class="country">France</div></div><div class="aff"><div class="institution">IFR62</div>, Lyon, F-69008, <div class="country">France</div></div> </div> <div class="info-author-correspondence"> <div content-id="cor1">Correspondence: Veronique Maguer-Satta, Ph.D., CR1 CNRS, Inserm, U590, Centre Leéon Beérard, 28 Rue Laennec, 69373 Lyon Cedex 08, France. Telephone: 33-0-4-78-78-29-74; Fax: 33-0-4-78-78-27-20; e-mail: <a href="mailto:maguer@lyon.fnclcc.fr" target="_blank">maguer@lyon.fnclcc.fr</a></div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/stmcls/search-results?f_Authors=Veronique+Maguer-Satta" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Maguer-Satta Veronique%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Roger Besançon</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Roger Besançon </div> </div> <div class="info-card-affilitation"> <div class="aff"><div class="institution">Université de Lyon</div>, Lyon, F-69007, <div class="country">France</div></div><div class="aff"><div class="institution">Inserm, U590, Centre Léon Bérard</div>, Lyon, F-69008, Lyon, <div class="country">France</div></div><div class="aff"><div class="institution">IFR62</div>, Lyon, F-69008, <div class="country">France</div></div><div class="aff"><div class="institution">Université de Lyon 1</div>, ISPB, F-69008, <div class="country">France</div></div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/stmcls/search-results?f_Authors=Roger+Besan%c3%a7on" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Besançon Roger%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Elodie Bachelard-Cascales</button><span class='delimiter'></span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_Abstract_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Elodie Bachelard-Cascales </div> </div> <div class="info-card-affilitation"> <div class="aff"><div class="institution">Université de Lyon</div>, Lyon, F-69007, <div class="country">France</div></div><div class="aff"><div class="institution">Inserm, U590, Centre Léon Bérard</div>, Lyon, F-69008, Lyon, <div class="country">France</div></div><div class="aff"><div class="institution">IFR62</div>, Lyon, F-69008, <div class="country">France</div></div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/stmcls/search-results?f_Authors=Elodie+Bachelard-Cascales" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Bachelard-Cascales Elodie%22">Google Scholar</a> </div> </div> </span> </span> </div> </div> <div class="pub-history-wrap clearfix js-history-dropdown-wrap"> <div class="pub-history-row clearfix"> <div class="ww-citation-primary"><em>Stem Cells</em>, Volume 29, Issue 3, March 2011, Pages 389–396, <a href='https://doi.org/10.1002/stem.592'>https://doi.org/10.1002/stem.592</a></div> </div> <div class="pub-history-row clearfix"> <div class="ww-citation-date-wrap"> <div class="citation-label">Published:</div> <div class="citation-date">21 March 2011</div> </div> <a href="javascript:;" class="history-label js-history-dropdown-trigger st-article-history at-ArticleHistory"> <span>Article history</span><i class="icon-general-arrow-filled-down arrow-icon"></i> </a> </div> <div class="ww-history js-history-entries-wrap at-history-entries-wrap"> <div class="history-entry at-history-entry"> <div class="wi-state">Received:</div> <div class="wi-date">05 October 2010</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Accepted:</div> <div class="wi-date">16 December 2010</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Published:</div> <div class="wi-date">21 March 2011</div> </div> </div> </div> </div> </div> <script> $(document).ready(function () { $('.article-top-widget').on('click', '.ati-toggle-trigger', function () { $(this).find('.icon-general-add, .icon-minus').toggleClass('icon-minus icon-general-add'); $(this).siblings('.ati-toggle-content').toggleClass('hide'); }); // In Chrome, an anchor tag with target="_blank" and a "mailto:" href opens a new tab/window as well as the email client // I suspect this behavior will be corrected in the future // Remove the target="_blank" 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First identified in leukemia as a tumor-specific antigen (common acute lymphoblastic leukemia antigen), CD10 has become largely used in cancer diagnosis. However, its function in oncogenesis remains unclear. We previously identified CD10 as a tool to access sphere-forming cells and showed its involvement in mammary stem cell (SC) regulation. We further illustrated that its enzymatic activity is involved, through signaling peptides, in SC maintenance. Therefore, CD10 is not only a cell surface marker in normal and malignant contexts but also affects the extracellular environment and plays a key role in regulation of a number of biological functions and likely in SC. In tumors, the “niche” favors the survival of sheltered cancer SC whose eradication has become the new challenge in oncology. This highlights the importance of understanding the role of CD10 in cancer SC. We will review the characteristics, main functions, and mechanism of action of CD10. Finally, we will review its clinical use and involvement in cancer.</p></section> <div class="article-metadata-panel clearfix at-ArticleMetadata"></div> <div class="kwd-group"><a class="kwd-part kwd-main" href="javascript:;" data-keyword=""CD10 enzyme"">CD10 enzyme</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword="cancer">cancer</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword="Microenvironment">Microenvironment</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword=""Stem cells"">Stem cells</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword="Signaling">Signaling</a></div>  <div class="widget widget-ArticlePubStateInfo widget-instance-OUP_ArticlePubStateInfo"> </div> <div class="article-metadata-standalone-panel clearfix"></div> <div class="copyright copyright-statement">Copyright © 2011 AlphaMed Press</div><div class="license"><div class="license-p">This article is published and distributed under the terms of the Oxford 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Concise Review: Neutral Endopeptidase (CD10): A Multifaceted Environment Actor in Stem Cells, Physiological Mechanisms, and Cancer | Stem Cells | Oxford Academic