AXL is an oncotarget in human colorectal cancer
AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing...
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| Veröffentlicht in: | Oncotarget 2015-09, Vol.6 (27), p.23281-23296 |
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| creator | Martinelli, Erika Martini, Giulia Cardone, Claudia Troiani, Teresa Liguori, Giuseppina Vitagliano, Donata Napolitano, Stefania Morgillo, Floriana Rinaldi, Barbara Melillo, Rosa Marina Liotti, Federica Nappi, Anna Bianco, Roberto Berrino, Liberato Ciuffreda, Loreta Pia Ciardiello, Davide Iaffaioli, Vincenzo Botti, Gerardo Ferraiolo, Fiorella Ciardiello, Fortunato |
| description | AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC. |
| doi_str_mv | 10.18632/oncotarget.3962 |
| format | Article |
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We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.3962</identifier><identifier>PMID: 25966280</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Anilides - chemistry ; Animals ; Antineoplastic Agents - chemistry ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Survival ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - metabolism ; Female ; Gene Silencing ; HCT116 Cells ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Intercellular Signaling Peptides and Proteins - metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Middle Aged ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins - chemistry ; Proto-Oncogene Proteins - metabolism ; Quinolines - chemistry ; Receptor Protein-Tyrosine Kinases - chemistry ; Receptor Protein-Tyrosine Kinases - metabolism ; Research Paper: Pathology ; RNA Interference</subject><ispartof>Oncotarget, 2015-09, Vol.6 (27), p.23281-23296</ispartof><rights>Copyright: © 2015 Martinelli et al. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-cddf6b21ad0a724d6c7216932e080a90dffa89869965e9b18af23e0541bd291d3</citedby><cites>FETCH-LOGICAL-c462t-cddf6b21ad0a724d6c7216932e080a90dffa89869965e9b18af23e0541bd291d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695118/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695118/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25966280$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martinelli, Erika</creatorcontrib><creatorcontrib>Martini, Giulia</creatorcontrib><creatorcontrib>Cardone, Claudia</creatorcontrib><creatorcontrib>Troiani, Teresa</creatorcontrib><creatorcontrib>Liguori, Giuseppina</creatorcontrib><creatorcontrib>Vitagliano, Donata</creatorcontrib><creatorcontrib>Napolitano, Stefania</creatorcontrib><creatorcontrib>Morgillo, Floriana</creatorcontrib><creatorcontrib>Rinaldi, Barbara</creatorcontrib><creatorcontrib>Melillo, Rosa Marina</creatorcontrib><creatorcontrib>Liotti, Federica</creatorcontrib><creatorcontrib>Nappi, Anna</creatorcontrib><creatorcontrib>Bianco, Roberto</creatorcontrib><creatorcontrib>Berrino, Liberato</creatorcontrib><creatorcontrib>Ciuffreda, Loreta Pia</creatorcontrib><creatorcontrib>Ciardiello, Davide</creatorcontrib><creatorcontrib>Iaffaioli, Vincenzo</creatorcontrib><creatorcontrib>Botti, Gerardo</creatorcontrib><creatorcontrib>Ferraiolo, Fiorella</creatorcontrib><creatorcontrib>Ciardiello, Fortunato</creatorcontrib><title>AXL is an oncotarget in human colorectal cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anilides - chemistry</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Female</subject><subject>Gene Silencing</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Neoplasm Transplantation</subject><subject>Neovascularization, Pathologic</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Proto-Oncogene Proteins - chemistry</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Quinolines - chemistry</subject><subject>Receptor Protein-Tyrosine Kinases - chemistry</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Research Paper: Pathology</subject><subject>RNA Interference</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUE1Lw0AQXUSxpfbuSXL0knY_ks3ORSjFLwh4UfC2bHY3bSTJ1t1E8N-b2trWucww896bx0PomuAZEZzRuWu165Rf2W7GgNMzNCaQQEzTlJ2fzCM0DeEDD5UmmaBwiUY0Bc6pwGM0X7znURUi1UZHuahqo3XfDDvtauet7lQdadVq66_QRanqYKf7PkFvD_evy6c4f3l8Xi7yWCecdrE2puQFJcpgldHEcJ1RwoFRiwVWgE1ZKgGCA_DUQkGEKimzg0FSGArEsAm62-lu-qKxRtu286qWG181yn9Lpyr5_9JWa7lyXzLhkBIiBoHbvYB3n70NnWyqoG1dq9a6PkiSbf0AzcgAxTuo9i4Eb8vDG4Llb9TymI3cRj1Qbk7tHQh_wbIf9iR8qA</recordid><startdate>20150915</startdate><enddate>20150915</enddate><creator>Martinelli, Erika</creator><creator>Martini, Giulia</creator><creator>Cardone, Claudia</creator><creator>Troiani, Teresa</creator><creator>Liguori, Giuseppina</creator><creator>Vitagliano, Donata</creator><creator>Napolitano, Stefania</creator><creator>Morgillo, Floriana</creator><creator>Rinaldi, Barbara</creator><creator>Melillo, Rosa Marina</creator><creator>Liotti, Federica</creator><creator>Nappi, Anna</creator><creator>Bianco, Roberto</creator><creator>Berrino, Liberato</creator><creator>Ciuffreda, Loreta Pia</creator><creator>Ciardiello, Davide</creator><creator>Iaffaioli, Vincenzo</creator><creator>Botti, Gerardo</creator><creator>Ferraiolo, Fiorella</creator><creator>Ciardiello, Fortunato</creator><general>Impact Journals LLC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150915</creationdate><title>AXL is an oncotarget in human colorectal cancer</title><author>Martinelli, Erika ; Martini, Giulia ; Cardone, Claudia ; Troiani, Teresa ; Liguori, Giuseppina ; Vitagliano, Donata ; Napolitano, Stefania ; Morgillo, Floriana ; Rinaldi, Barbara ; Melillo, Rosa Marina ; Liotti, Federica ; Nappi, Anna ; Bianco, Roberto ; Berrino, Liberato ; Ciuffreda, Loreta Pia ; Ciardiello, Davide ; Iaffaioli, Vincenzo ; Botti, Gerardo ; Ferraiolo, Fiorella ; Ciardiello, Fortunato</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-cddf6b21ad0a724d6c7216932e080a90dffa89869965e9b18af23e0541bd291d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anilides - chemistry</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Colorectal Neoplasms - drug therapy</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Female</topic><topic>Gene Silencing</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Neoplasm Transplantation</topic><topic>Neovascularization, Pathologic</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Proto-Oncogene Proteins - chemistry</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Quinolines - chemistry</topic><topic>Receptor Protein-Tyrosine Kinases - chemistry</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Research Paper: Pathology</topic><topic>RNA Interference</topic><toplevel>online_resources</toplevel><creatorcontrib>Martinelli, Erika</creatorcontrib><creatorcontrib>Martini, Giulia</creatorcontrib><creatorcontrib>Cardone, Claudia</creatorcontrib><creatorcontrib>Troiani, Teresa</creatorcontrib><creatorcontrib>Liguori, Giuseppina</creatorcontrib><creatorcontrib>Vitagliano, Donata</creatorcontrib><creatorcontrib>Napolitano, Stefania</creatorcontrib><creatorcontrib>Morgillo, Floriana</creatorcontrib><creatorcontrib>Rinaldi, Barbara</creatorcontrib><creatorcontrib>Melillo, Rosa Marina</creatorcontrib><creatorcontrib>Liotti, Federica</creatorcontrib><creatorcontrib>Nappi, Anna</creatorcontrib><creatorcontrib>Bianco, Roberto</creatorcontrib><creatorcontrib>Berrino, Liberato</creatorcontrib><creatorcontrib>Ciuffreda, Loreta Pia</creatorcontrib><creatorcontrib>Ciardiello, Davide</creatorcontrib><creatorcontrib>Iaffaioli, Vincenzo</creatorcontrib><creatorcontrib>Botti, Gerardo</creatorcontrib><creatorcontrib>Ferraiolo, Fiorella</creatorcontrib><creatorcontrib>Ciardiello, Fortunato</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martinelli, Erika</au><au>Martini, Giulia</au><au>Cardone, Claudia</au><au>Troiani, Teresa</au><au>Liguori, Giuseppina</au><au>Vitagliano, Donata</au><au>Napolitano, Stefania</au><au>Morgillo, Floriana</au><au>Rinaldi, Barbara</au><au>Melillo, Rosa Marina</au><au>Liotti, Federica</au><au>Nappi, Anna</au><au>Bianco, Roberto</au><au>Berrino, Liberato</au><au>Ciuffreda, Loreta Pia</au><au>Ciardiello, Davide</au><au>Iaffaioli, Vincenzo</au><au>Botti, Gerardo</au><au>Ferraiolo, Fiorella</au><au>Ciardiello, Fortunato</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AXL is an oncotarget in human colorectal cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2015-09-15</date><risdate>2015</risdate><volume>6</volume><issue>27</issue><spage>23281</spage><epage>23296</epage><pages>23281-23296</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>25966280</pmid><doi>10.18632/oncotarget.3962</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| source | Freely Accessible Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Adult Aged Aged, 80 and over Anilides - chemistry Animals Antineoplastic Agents - chemistry Cell Line, Tumor Cell Movement Cell Proliferation Cell Survival Colorectal Neoplasms - drug therapy Colorectal Neoplasms - metabolism Female Gene Silencing HCT116 Cells Humans Immunohistochemistry In Situ Hybridization, Fluorescence Intercellular Signaling Peptides and Proteins - metabolism Male Mice Mice, Inbred BALB C Mice, Nude Middle Aged Neoplasm Transplantation Neovascularization, Pathologic Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins - chemistry Proto-Oncogene Proteins - metabolism Quinolines - chemistry Receptor Protein-Tyrosine Kinases - chemistry Receptor Protein-Tyrosine Kinases - metabolism Research Paper: Pathology RNA Interference |
| title | AXL is an oncotarget in human colorectal cancer |
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