Evidence for a role of E-cadherin in suppressing liver carcinogenesis in mice and men
The cell adhesion molecule E-cadherin has critical functions in development and carcinogenesis. Impaired expression of E-cadherin has been associated with disrupted tissue homeostasis, progression of cancer and a worse patient prognosis. So far, the role of E-cadherin in homeostasis and carcinogenes...
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| Veröffentlicht in: | Carcinogenesis (New York) 2014-08, Vol.35 (8), p.1855-1862 |
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| creator | Schneider, Marlon R Hiltwein, Felix Grill, Jessica Blum, Helmut Krebs, Stefan Klanner, Andrea Bauersachs, Stefan Bruns, Christiane Longerich, Thomas Horst, David Brandl, Lydia de Toni, Enrico Herbst, Andreas Kolligs, Frank T |
| description | The cell adhesion molecule E-cadherin has critical functions in development and carcinogenesis. Impaired expression of E-cadherin has been associated with disrupted tissue homeostasis, progression of cancer and a worse patient prognosis. So far, the role of E-cadherin in homeostasis and carcinogenesis of the liver is not well understood. By use of a mouse model with liver-specific deletion of E-cadherin and administration of the carcinogen diethylnitrosamine, we demonstrate that loss of E-cadherin expression in hepatocytes results in acceleration of the growth of hepatocellular carcinoma (HCC). In contrast, liver regeneration is not disturbed in mice lacking E-cadherin expression in hepatocytes. In human HCC, we observed four different expression patterns of E-cadherin. Notably, atypical cytosolic expression of E-cadherin was positively correlated with a poorer patient prognosis. The median overall survival of patients with HCC expressing E-cadherin on the membrane only was 221 weeks (95% confidence interval: 51-391) compared with 131 weeks in patients with cytosolic expression (95% confidence interval: 71-191 weeks; P < 0.05). In conclusion, we demonstrate that impaired expression of E-cadherin promotes hepatocellular carcinogenesis and is associated with a worse prognosis in humans. |
| doi_str_mv | 10.1093/carcin/bgu109 |
| format | Article |
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Impaired expression of E-cadherin has been associated with disrupted tissue homeostasis, progression of cancer and a worse patient prognosis. So far, the role of E-cadherin in homeostasis and carcinogenesis of the liver is not well understood. By use of a mouse model with liver-specific deletion of E-cadherin and administration of the carcinogen diethylnitrosamine, we demonstrate that loss of E-cadherin expression in hepatocytes results in acceleration of the growth of hepatocellular carcinoma (HCC). In contrast, liver regeneration is not disturbed in mice lacking E-cadherin expression in hepatocytes. In human HCC, we observed four different expression patterns of E-cadherin. Notably, atypical cytosolic expression of E-cadherin was positively correlated with a poorer patient prognosis. The median overall survival of patients with HCC expressing E-cadherin on the membrane only was 221 weeks (95% confidence interval: 51-391) compared with 131 weeks in patients with cytosolic expression (95% confidence interval: 71-191 weeks; P < 0.05). In conclusion, we demonstrate that impaired expression of E-cadherin promotes hepatocellular carcinogenesis and is associated with a worse prognosis in humans.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgu109</identifier><identifier>PMID: 24840851</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Apoptosis ; Blotting, Western ; Cadherins - genetics ; Cadherins - metabolism ; Carcinogenesis - genetics ; Carcinogenesis - pathology ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - prevention & control ; Cdh1 Proteins - physiology ; Cell Proliferation ; Female ; Humans ; Immunoenzyme Techniques ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Liver Neoplasms - prevention & control ; Liver Regeneration ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Tumor Cells, Cultured</subject><ispartof>Carcinogenesis (New York), 2014-08, Vol.35 (8), p.1855-1862</ispartof><rights>The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-e8536578e7c363997349b0e44d246580fdf6ce3d2bed2ba3ef2a6d8a58e10aae3</citedby><cites>FETCH-LOGICAL-c398t-e8536578e7c363997349b0e44d246580fdf6ce3d2bed2ba3ef2a6d8a58e10aae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24840851$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schneider, Marlon R</creatorcontrib><creatorcontrib>Hiltwein, Felix</creatorcontrib><creatorcontrib>Grill, Jessica</creatorcontrib><creatorcontrib>Blum, Helmut</creatorcontrib><creatorcontrib>Krebs, Stefan</creatorcontrib><creatorcontrib>Klanner, Andrea</creatorcontrib><creatorcontrib>Bauersachs, Stefan</creatorcontrib><creatorcontrib>Bruns, Christiane</creatorcontrib><creatorcontrib>Longerich, Thomas</creatorcontrib><creatorcontrib>Horst, David</creatorcontrib><creatorcontrib>Brandl, Lydia</creatorcontrib><creatorcontrib>de Toni, Enrico</creatorcontrib><creatorcontrib>Herbst, Andreas</creatorcontrib><creatorcontrib>Kolligs, Frank T</creatorcontrib><title>Evidence for a role of E-cadherin in suppressing liver carcinogenesis in mice and men</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>The cell adhesion molecule E-cadherin has critical functions in development and carcinogenesis. Impaired expression of E-cadherin has been associated with disrupted tissue homeostasis, progression of cancer and a worse patient prognosis. So far, the role of E-cadherin in homeostasis and carcinogenesis of the liver is not well understood. By use of a mouse model with liver-specific deletion of E-cadherin and administration of the carcinogen diethylnitrosamine, we demonstrate that loss of E-cadherin expression in hepatocytes results in acceleration of the growth of hepatocellular carcinoma (HCC). In contrast, liver regeneration is not disturbed in mice lacking E-cadherin expression in hepatocytes. In human HCC, we observed four different expression patterns of E-cadherin. Notably, atypical cytosolic expression of E-cadherin was positively correlated with a poorer patient prognosis. The median overall survival of patients with HCC expressing E-cadherin on the membrane only was 221 weeks (95% confidence interval: 51-391) compared with 131 weeks in patients with cytosolic expression (95% confidence interval: 71-191 weeks; P < 0.05). In conclusion, we demonstrate that impaired expression of E-cadherin promotes hepatocellular carcinogenesis and is associated with a worse prognosis in humans.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Blotting, Western</subject><subject>Cadherins - genetics</subject><subject>Cadherins - metabolism</subject><subject>Carcinogenesis - genetics</subject><subject>Carcinogenesis - pathology</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - prevention & control</subject><subject>Cdh1 Proteins - physiology</subject><subject>Cell Proliferation</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - prevention & control</subject><subject>Liver Regeneration</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Tumor Cells, Cultured</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kFFLwzAQx4Mobk4ffZV8gbikl2bpo4w5hYEv7rmkyWVG1rQkduC3t6Mq3HEc_Pjf8SPkXvBHwStYWpNsiMvmMIzrBZkLqTgrhOaXZM6FBAYAckZucv7kXCgoq2syK6SWXJdiTvabU3AYLVLfJWpo6o5IO083zBr3gSlEOlYe-j5hziEe6DGcMNHpbHfAiDnkM9OGMcRER1uMt-TKm2PGu9-5IPvnzfv6he3etq_rpx2zUOkvhroEVa40riwoqKoVyKrhKKUrpCo1984ri-CKBsc2gL4wymlTahTcGIQFYVOuTV3OCX3dp9Ca9F0LXp_11NOf9aRn5B8mvh-aFt0__ecDfgDQiGNW</recordid><startdate>20140801</startdate><enddate>20140801</enddate><creator>Schneider, Marlon R</creator><creator>Hiltwein, Felix</creator><creator>Grill, Jessica</creator><creator>Blum, Helmut</creator><creator>Krebs, Stefan</creator><creator>Klanner, Andrea</creator><creator>Bauersachs, Stefan</creator><creator>Bruns, Christiane</creator><creator>Longerich, Thomas</creator><creator>Horst, David</creator><creator>Brandl, Lydia</creator><creator>de Toni, Enrico</creator><creator>Herbst, Andreas</creator><creator>Kolligs, Frank T</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20140801</creationdate><title>Evidence for a role of E-cadherin in suppressing liver carcinogenesis in mice and men</title><author>Schneider, Marlon R ; Hiltwein, Felix ; Grill, Jessica ; Blum, Helmut ; Krebs, Stefan ; Klanner, Andrea ; Bauersachs, Stefan ; Bruns, Christiane ; Longerich, Thomas ; Horst, David ; Brandl, Lydia ; de Toni, Enrico ; Herbst, Andreas ; Kolligs, Frank T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-e8536578e7c363997349b0e44d246580fdf6ce3d2bed2ba3ef2a6d8a58e10aae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Blotting, Western</topic><topic>Cadherins - genetics</topic><topic>Cadherins - metabolism</topic><topic>Carcinogenesis - genetics</topic><topic>Carcinogenesis - pathology</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - prevention & control</topic><topic>Cdh1 Proteins - physiology</topic><topic>Cell Proliferation</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - prevention & control</topic><topic>Liver Regeneration</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schneider, Marlon R</creatorcontrib><creatorcontrib>Hiltwein, Felix</creatorcontrib><creatorcontrib>Grill, Jessica</creatorcontrib><creatorcontrib>Blum, Helmut</creatorcontrib><creatorcontrib>Krebs, Stefan</creatorcontrib><creatorcontrib>Klanner, Andrea</creatorcontrib><creatorcontrib>Bauersachs, Stefan</creatorcontrib><creatorcontrib>Bruns, Christiane</creatorcontrib><creatorcontrib>Longerich, Thomas</creatorcontrib><creatorcontrib>Horst, David</creatorcontrib><creatorcontrib>Brandl, Lydia</creatorcontrib><creatorcontrib>de Toni, Enrico</creatorcontrib><creatorcontrib>Herbst, Andreas</creatorcontrib><creatorcontrib>Kolligs, Frank T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schneider, Marlon R</au><au>Hiltwein, Felix</au><au>Grill, Jessica</au><au>Blum, Helmut</au><au>Krebs, Stefan</au><au>Klanner, Andrea</au><au>Bauersachs, Stefan</au><au>Bruns, Christiane</au><au>Longerich, Thomas</au><au>Horst, David</au><au>Brandl, Lydia</au><au>de Toni, Enrico</au><au>Herbst, Andreas</au><au>Kolligs, Frank T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence for a role of E-cadherin in suppressing liver carcinogenesis in mice and men</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2014-08-01</date><risdate>2014</risdate><volume>35</volume><issue>8</issue><spage>1855</spage><epage>1862</epage><pages>1855-1862</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><abstract>The cell adhesion molecule E-cadherin has critical functions in development and carcinogenesis. Impaired expression of E-cadherin has been associated with disrupted tissue homeostasis, progression of cancer and a worse patient prognosis. So far, the role of E-cadherin in homeostasis and carcinogenesis of the liver is not well understood. By use of a mouse model with liver-specific deletion of E-cadherin and administration of the carcinogen diethylnitrosamine, we demonstrate that loss of E-cadherin expression in hepatocytes results in acceleration of the growth of hepatocellular carcinoma (HCC). In contrast, liver regeneration is not disturbed in mice lacking E-cadherin expression in hepatocytes. In human HCC, we observed four different expression patterns of E-cadherin. Notably, atypical cytosolic expression of E-cadherin was positively correlated with a poorer patient prognosis. The median overall survival of patients with HCC expressing E-cadherin on the membrane only was 221 weeks (95% confidence interval: 51-391) compared with 131 weeks in patients with cytosolic expression (95% confidence interval: 71-191 weeks; P < 0.05). In conclusion, we demonstrate that impaired expression of E-cadherin promotes hepatocellular carcinogenesis and is associated with a worse prognosis in humans.</abstract><cop>England</cop><pmid>24840851</pmid><doi>10.1093/carcin/bgu109</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals Current; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Apoptosis Blotting, Western Cadherins - genetics Cadherins - metabolism Carcinogenesis - genetics Carcinogenesis - pathology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - prevention & control Cdh1 Proteins - physiology Cell Proliferation Female Humans Immunoenzyme Techniques Liver Neoplasms - genetics Liver Neoplasms - pathology Liver Neoplasms - prevention & control Liver Regeneration Male Mice Mice, Inbred C57BL Mice, Knockout Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Tumor Cells, Cultured |
| title | Evidence for a role of E-cadherin in suppressing liver carcinogenesis in mice and men |
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