High expression of the Notch ligand Jagged‐1 is associated with poor prognosis after surgery for colorectal cancer
The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged‐1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expre...
Gespeichert in:
| Veröffentlicht in: | Cancer science 2016-11, Vol.107 (11), p.1705-1716 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1716 |
|---|---|
| container_issue | 11 |
| container_start_page | 1705 |
| container_title | Cancer science |
| container_volume | 107 |
| creator | Sugiyama, Masakazu Oki, Eiji Nakaji, Yu Tsutsumi, Satoshi Ono, Naomi Nakanishi, Ryota Sugiyama, Masahiko Nakashima, Yuichiro Sonoda, Hideto Ohgaki, Kippei Yamashita, Nami Saeki, Hiroshi Okano, Shinji Kitao, Hiroyuki Morita, Masaru Oda, Yoshinao Maehara, Yoshihiko |
| description | The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged‐1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E‐cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse‐free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E‐cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E‐cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E‐cadherin expression. In vitro studies suggested that RAS‐MEK‐MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.
This is the first report demonstrating the poor prognostic significance of JAG1 expression in CRC. Combination of high JAG1 expression with low E‐cadherin expression leads to severely poor outcome. Novel insight into the correlation between KRAS status and JAG1 expression in CRC patients. |
| doi_str_mv | 10.1111/cas.13075 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5132269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1850770897</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5005-42c91d4128c64fb3905e49cba4b2df7ab71c87428d12fb6172aafde497542c9b3</originalsourceid><addsrcrecordid>eNp1kcFu1DAURS1ERUthwQ8gS2zoIq3t2HG8QapGLaWqYAGsLcd5SVxl4mA7LbPrJ_CNfAmeTqkACW9s6R4fvaeL0CtKjmk-J9bEY1oSKZ6gA1pyVUhCqqf3b1koUrJ99DzGa0LKiiv-DO0zKWrFZX2A0oXrBwzf5wAxOj9h3-E0AP7okx3w6HoztfjS9D20P-9-UOwiNjF660yCFt-6NODZ-4Dn4PvJx23cJQg4LqGHsMFdzqwffQCbzIitmSyEF2ivM2OElw_3Ifp6fvZldVFcfXr_YXV6VVhBiCg4s4q2nLLaVrxrSkUEcGUbwxvWdtI0ktpacla3lHVNRSUzpmszIsX2a1Meonc777w0a2gtTCmYUc_BrU3YaG-c_juZ3KB7f6MFLRmrVBa8fRAE_22BmPTaRQvjaCbwS9S0FkRKUiuZ0Tf_oNd-CVNeTzOmCBOS8SpTRzvKBh9jgO5xGEr0tkudu9T3XWb29Z_TP5K_y8vAyQ64dSNs_m_Sq9PPO-Uvbh6rPg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2290257246</pqid></control><display><type>article</type><title>High expression of the Notch ligand Jagged‐1 is associated with poor prognosis after surgery for colorectal cancer</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><creator>Sugiyama, Masakazu ; Oki, Eiji ; Nakaji, Yu ; Tsutsumi, Satoshi ; Ono, Naomi ; Nakanishi, Ryota ; Sugiyama, Masahiko ; Nakashima, Yuichiro ; Sonoda, Hideto ; Ohgaki, Kippei ; Yamashita, Nami ; Saeki, Hiroshi ; Okano, Shinji ; Kitao, Hiroyuki ; Morita, Masaru ; Oda, Yoshinao ; Maehara, Yoshihiko</creator><creatorcontrib>Sugiyama, Masakazu ; Oki, Eiji ; Nakaji, Yu ; Tsutsumi, Satoshi ; Ono, Naomi ; Nakanishi, Ryota ; Sugiyama, Masahiko ; Nakashima, Yuichiro ; Sonoda, Hideto ; Ohgaki, Kippei ; Yamashita, Nami ; Saeki, Hiroshi ; Okano, Shinji ; Kitao, Hiroyuki ; Morita, Masaru ; Oda, Yoshinao ; Maehara, Yoshihiko</creatorcontrib><description>The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged‐1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E‐cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse‐free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E‐cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E‐cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E‐cadherin expression. In vitro studies suggested that RAS‐MEK‐MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.
This is the first report demonstrating the poor prognostic significance of JAG1 expression in CRC. Combination of high JAG1 expression with low E‐cadherin expression leads to severely poor outcome. Novel insight into the correlation between KRAS status and JAG1 expression in CRC patients.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.13075</identifier><identifier>PMID: 27589478</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Cadherins - metabolism ; Carcinogenesis ; Cell adhesion & migration ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Colon cancer ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - diagnosis ; Colorectal Neoplasms - metabolism ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - surgery ; Endothelium ; Endothelium - metabolism ; Epithelial-Mesenchymal Transition ; Gene silencing ; Humans ; Immunohistochemistry ; Intracellular signalling ; Investigations ; JAG1 ; Jagged-1 Protein - metabolism ; Kaplan-Meier Estimate ; Kinases ; Ligands ; MAP kinase ; Medical prognosis ; Mesenchyme ; Multivariate analysis ; Mutation ; Notch ; Original ; Pharmaceuticals ; Prognosis ; Receptors, Notch - metabolism ; Signal transduction ; siRNA ; Surgery ; survival rate ; Wnt protein</subject><ispartof>Cancer science, 2016-11, Vol.107 (11), p.1705-1716</ispartof><rights>2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2016. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5005-42c91d4128c64fb3905e49cba4b2df7ab71c87428d12fb6172aafde497542c9b3</citedby><cites>FETCH-LOGICAL-c5005-42c91d4128c64fb3905e49cba4b2df7ab71c87428d12fb6172aafde497542c9b3</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/PMC5132269/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132269/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27589478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sugiyama, Masakazu</creatorcontrib><creatorcontrib>Oki, Eiji</creatorcontrib><creatorcontrib>Nakaji, Yu</creatorcontrib><creatorcontrib>Tsutsumi, Satoshi</creatorcontrib><creatorcontrib>Ono, Naomi</creatorcontrib><creatorcontrib>Nakanishi, Ryota</creatorcontrib><creatorcontrib>Sugiyama, Masahiko</creatorcontrib><creatorcontrib>Nakashima, Yuichiro</creatorcontrib><creatorcontrib>Sonoda, Hideto</creatorcontrib><creatorcontrib>Ohgaki, Kippei</creatorcontrib><creatorcontrib>Yamashita, Nami</creatorcontrib><creatorcontrib>Saeki, Hiroshi</creatorcontrib><creatorcontrib>Okano, Shinji</creatorcontrib><creatorcontrib>Kitao, Hiroyuki</creatorcontrib><creatorcontrib>Morita, Masaru</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><creatorcontrib>Maehara, Yoshihiko</creatorcontrib><title>High expression of the Notch ligand Jagged‐1 is associated with poor prognosis after surgery for colorectal cancer</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged‐1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E‐cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse‐free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E‐cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E‐cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E‐cadherin expression. In vitro studies suggested that RAS‐MEK‐MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.
This is the first report demonstrating the poor prognostic significance of JAG1 expression in CRC. Combination of high JAG1 expression with low E‐cadherin expression leads to severely poor outcome. Novel insight into the correlation between KRAS status and JAG1 expression in CRC patients.</description><subject>Cadherins - metabolism</subject><subject>Carcinogenesis</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - diagnosis</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - surgery</subject><subject>Endothelium</subject><subject>Endothelium - metabolism</subject><subject>Epithelial-Mesenchymal Transition</subject><subject>Gene silencing</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intracellular signalling</subject><subject>Investigations</subject><subject>JAG1</subject><subject>Jagged-1 Protein - metabolism</subject><subject>Kaplan-Meier Estimate</subject><subject>Kinases</subject><subject>Ligands</subject><subject>MAP kinase</subject><subject>Medical prognosis</subject><subject>Mesenchyme</subject><subject>Multivariate analysis</subject><subject>Mutation</subject><subject>Notch</subject><subject>Original</subject><subject>Pharmaceuticals</subject><subject>Prognosis</subject><subject>Receptors, Notch - metabolism</subject><subject>Signal transduction</subject><subject>siRNA</subject><subject>Surgery</subject><subject>survival rate</subject><subject>Wnt protein</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcFu1DAURS1ERUthwQ8gS2zoIq3t2HG8QapGLaWqYAGsLcd5SVxl4mA7LbPrJ_CNfAmeTqkACW9s6R4fvaeL0CtKjmk-J9bEY1oSKZ6gA1pyVUhCqqf3b1koUrJ99DzGa0LKiiv-DO0zKWrFZX2A0oXrBwzf5wAxOj9h3-E0AP7okx3w6HoztfjS9D20P-9-UOwiNjF660yCFt-6NODZ-4Dn4PvJx23cJQg4LqGHsMFdzqwffQCbzIitmSyEF2ivM2OElw_3Ifp6fvZldVFcfXr_YXV6VVhBiCg4s4q2nLLaVrxrSkUEcGUbwxvWdtI0ktpacla3lHVNRSUzpmszIsX2a1Meonc777w0a2gtTCmYUc_BrU3YaG-c_juZ3KB7f6MFLRmrVBa8fRAE_22BmPTaRQvjaCbwS9S0FkRKUiuZ0Tf_oNd-CVNeTzOmCBOS8SpTRzvKBh9jgO5xGEr0tkudu9T3XWb29Z_TP5K_y8vAyQ64dSNs_m_Sq9PPO-Uvbh6rPg</recordid><startdate>201611</startdate><enddate>201611</enddate><creator>Sugiyama, Masakazu</creator><creator>Oki, Eiji</creator><creator>Nakaji, Yu</creator><creator>Tsutsumi, Satoshi</creator><creator>Ono, Naomi</creator><creator>Nakanishi, Ryota</creator><creator>Sugiyama, Masahiko</creator><creator>Nakashima, Yuichiro</creator><creator>Sonoda, Hideto</creator><creator>Ohgaki, Kippei</creator><creator>Yamashita, Nami</creator><creator>Saeki, Hiroshi</creator><creator>Okano, Shinji</creator><creator>Kitao, Hiroyuki</creator><creator>Morita, Masaru</creator><creator>Oda, Yoshinao</creator><creator>Maehara, Yoshihiko</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><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>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>201611</creationdate><title>High expression of the Notch ligand Jagged‐1 is associated with poor prognosis after surgery for colorectal cancer</title><author>Sugiyama, Masakazu ; Oki, Eiji ; Nakaji, Yu ; Tsutsumi, Satoshi ; Ono, Naomi ; Nakanishi, Ryota ; Sugiyama, Masahiko ; Nakashima, Yuichiro ; Sonoda, Hideto ; Ohgaki, Kippei ; Yamashita, Nami ; Saeki, Hiroshi ; Okano, Shinji ; Kitao, Hiroyuki ; Morita, Masaru ; Oda, Yoshinao ; Maehara, Yoshihiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5005-42c91d4128c64fb3905e49cba4b2df7ab71c87428d12fb6172aafde497542c9b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cadherins - metabolism</topic><topic>Carcinogenesis</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Colon cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - diagnosis</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Colorectal Neoplasms - surgery</topic><topic>Endothelium</topic><topic>Endothelium - metabolism</topic><topic>Epithelial-Mesenchymal Transition</topic><topic>Gene silencing</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intracellular signalling</topic><topic>Investigations</topic><topic>JAG1</topic><topic>Jagged-1 Protein - metabolism</topic><topic>Kaplan-Meier Estimate</topic><topic>Kinases</topic><topic>Ligands</topic><topic>MAP kinase</topic><topic>Medical prognosis</topic><topic>Mesenchyme</topic><topic>Multivariate analysis</topic><topic>Mutation</topic><topic>Notch</topic><topic>Original</topic><topic>Pharmaceuticals</topic><topic>Prognosis</topic><topic>Receptors, Notch - metabolism</topic><topic>Signal transduction</topic><topic>siRNA</topic><topic>Surgery</topic><topic>survival rate</topic><topic>Wnt protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sugiyama, Masakazu</creatorcontrib><creatorcontrib>Oki, Eiji</creatorcontrib><creatorcontrib>Nakaji, Yu</creatorcontrib><creatorcontrib>Tsutsumi, Satoshi</creatorcontrib><creatorcontrib>Ono, Naomi</creatorcontrib><creatorcontrib>Nakanishi, Ryota</creatorcontrib><creatorcontrib>Sugiyama, Masahiko</creatorcontrib><creatorcontrib>Nakashima, Yuichiro</creatorcontrib><creatorcontrib>Sonoda, Hideto</creatorcontrib><creatorcontrib>Ohgaki, Kippei</creatorcontrib><creatorcontrib>Yamashita, Nami</creatorcontrib><creatorcontrib>Saeki, Hiroshi</creatorcontrib><creatorcontrib>Okano, Shinji</creatorcontrib><creatorcontrib>Kitao, Hiroyuki</creatorcontrib><creatorcontrib>Morita, Masaru</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><creatorcontrib>Maehara, Yoshihiko</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sugiyama, Masakazu</au><au>Oki, Eiji</au><au>Nakaji, Yu</au><au>Tsutsumi, Satoshi</au><au>Ono, Naomi</au><au>Nakanishi, Ryota</au><au>Sugiyama, Masahiko</au><au>Nakashima, Yuichiro</au><au>Sonoda, Hideto</au><au>Ohgaki, Kippei</au><au>Yamashita, Nami</au><au>Saeki, Hiroshi</au><au>Okano, Shinji</au><au>Kitao, Hiroyuki</au><au>Morita, Masaru</au><au>Oda, Yoshinao</au><au>Maehara, Yoshihiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High expression of the Notch ligand Jagged‐1 is associated with poor prognosis after surgery for colorectal cancer</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2016-11</date><risdate>2016</risdate><volume>107</volume><issue>11</issue><spage>1705</spage><epage>1716</epage><pages>1705-1716</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged‐1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E‐cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse‐free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E‐cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E‐cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E‐cadherin expression. In vitro studies suggested that RAS‐MEK‐MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.
This is the first report demonstrating the poor prognostic significance of JAG1 expression in CRC. Combination of high JAG1 expression with low E‐cadherin expression leads to severely poor outcome. Novel insight into the correlation between KRAS status and JAG1 expression in CRC patients.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>27589478</pmid><doi>10.1111/cas.13075</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1347-9032 |
| ispartof | Cancer science, 2016-11, Vol.107 (11), p.1705-1716 |
| issn | 1347-9032 1349-7006 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5132269 |
| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; PubMed Central |
| subjects | Cadherins - metabolism Carcinogenesis Cell adhesion & migration Cell Line, Tumor Cell Proliferation Cell Survival Colon cancer Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - diagnosis Colorectal Neoplasms - metabolism Colorectal Neoplasms - pathology Colorectal Neoplasms - surgery Endothelium Endothelium - metabolism Epithelial-Mesenchymal Transition Gene silencing Humans Immunohistochemistry Intracellular signalling Investigations JAG1 Jagged-1 Protein - metabolism Kaplan-Meier Estimate Kinases Ligands MAP kinase Medical prognosis Mesenchyme Multivariate analysis Mutation Notch Original Pharmaceuticals Prognosis Receptors, Notch - metabolism Signal transduction siRNA Surgery survival rate Wnt protein |
| title | High expression of the Notch ligand Jagged‐1 is associated with poor prognosis after surgery for colorectal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T23%3A25%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20expression%20of%20the%20Notch%20ligand%20Jagged%E2%80%901%20is%20associated%20with%20poor%20prognosis%20after%20surgery%20for%20colorectal%20cancer&rft.jtitle=Cancer%20science&rft.au=Sugiyama,%20Masakazu&rft.date=2016-11&rft.volume=107&rft.issue=11&rft.spage=1705&rft.epage=1716&rft.pages=1705-1716&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.13075&rft_dat=%3Cproquest_pubme%3E1850770897%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2290257246&rft_id=info:pmid/27589478&rfr_iscdi=true |