The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma
RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of be...
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| Veröffentlicht in: | Tumor biology 2016, Vol.37 (1), p.627-631 |
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| creator | Wang, Dadong Tan, Jingwang Xu, Yong Han, Mingming Tu, Yuliang Zhu, Ziman Dou, Chunqing Xin, Jin Tan, Xianglong Zeng, Jian-ping Zhao, Gang Liu, Zhiwei |
| description | RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma. |
| doi_str_mv | 10.1007/s13277-015-3499-7 |
| format | Article |
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RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma.</description><identifier>ISSN: 1010-4283</identifier><identifier>EISSN: 1423-0380</identifier><identifier>DOI: 10.1007/s13277-015-3499-7</identifier><identifier>PMID: 26240024</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Adenocarcinoma in Situ - genetics ; Adenocarcinoma in Situ - metabolism ; Adenocarcinoma in Situ - pathology ; Aged ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - metabolism ; Carcinoma, Pancreatic Ductal - pathology ; Case-Control Studies ; Cell Line, Tumor ; Cell Membrane - metabolism ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Female ; Frizzled Receptors - genetics ; Frizzled Receptors - metabolism ; Gene Expression ; Humans ; Male ; Membranes ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Oncogene Proteins - genetics ; Oncogene Proteins - metabolism ; Pancreatic cancer ; Pancreatic Neoplasms ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - pathology ; Proteins ; Research Article ; Tissues ; Ubiquitin-Protein Ligases</subject><ispartof>Tumor biology, 2016, Vol.37 (1), p.627-631</ispartof><rights>International Society of Oncology and BioMarkers (ISOBM) 2015</rights><rights>International Society of Oncology and BioMarkers (ISOBM) 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-11e167368e9ae7e2235fcff6fd525e8c0a39357d65d59761e6af93002743d3a63</citedby><cites>FETCH-LOGICAL-c372t-11e167368e9ae7e2235fcff6fd525e8c0a39357d65d59761e6af93002743d3a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13277-015-3499-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13277-015-3499-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27933,27934,41497,42566,51328</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26240024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Dadong</creatorcontrib><creatorcontrib>Tan, Jingwang</creatorcontrib><creatorcontrib>Xu, Yong</creatorcontrib><creatorcontrib>Han, Mingming</creatorcontrib><creatorcontrib>Tu, Yuliang</creatorcontrib><creatorcontrib>Zhu, Ziman</creatorcontrib><creatorcontrib>Dou, Chunqing</creatorcontrib><creatorcontrib>Xin, Jin</creatorcontrib><creatorcontrib>Tan, Xianglong</creatorcontrib><creatorcontrib>Zeng, Jian-ping</creatorcontrib><creatorcontrib>Zhao, Gang</creatorcontrib><creatorcontrib>Liu, Zhiwei</creatorcontrib><title>The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma</title><title>Tumor biology</title><addtitle>Tumor Biol</addtitle><addtitle>Tumour Biol</addtitle><description>RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma.</description><subject>Adenocarcinoma in Situ - genetics</subject><subject>Adenocarcinoma in Situ - metabolism</subject><subject>Adenocarcinoma in Situ - pathology</subject><subject>Aged</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - metabolism</subject><subject>Carcinoma, Pancreatic Ductal - pathology</subject><subject>Case-Control Studies</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Frizzled Receptors - genetics</subject><subject>Frizzled Receptors - metabolism</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Male</subject><subject>Membranes</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Oncogene Proteins - genetics</subject><subject>Oncogene Proteins - metabolism</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Proteins</subject><subject>Research Article</subject><subject>Tissues</subject><subject>Ubiquitin-Protein Ligases</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtLHTEUx4O0-Go_gBsJdD2ax0wyWRbxBWKh2HXITU6ukZlkTGawdeVHb67XipuuzoH_43B-CB1RckIJkaeFciZlQ2jX8FapRu6gfdoy3hDek091J5Q0Lev5Hjoo5YFUo1JiF-0xwVpCWLuPXu7uAS-r8LiEOUQ8hLUpgH_eXrQcu_QUM6yXwcwhRRyizVDVgkcYV9lEwPB7ylDKRk0e-xyenwdwOIOFaU65RvBkXmNzsNgtdjYDNg5isibbENNovqDP3gwFvr7NQ_Tr4vzu7Kq5-XF5ffb9prFcsrmhFKiQXPSgDEhgjHfeei-861gHvSWGK95JJzrXKSkoCOMVrz_KljtuBD9E37a9U06PC5RZP6Qlx3pSU9lzIZgSfXXRrcvmVEoGr6ccRpP_aEr0hrneMtcVpd4w17Jmjt-al9UI7j3xD3I1sK2hVCmuIX84_d_WvxIqjio</recordid><startdate>2016</startdate><enddate>2016</enddate><creator>Wang, Dadong</creator><creator>Tan, Jingwang</creator><creator>Xu, Yong</creator><creator>Han, Mingming</creator><creator>Tu, Yuliang</creator><creator>Zhu, Ziman</creator><creator>Dou, Chunqing</creator><creator>Xin, Jin</creator><creator>Tan, Xianglong</creator><creator>Zeng, Jian-ping</creator><creator>Zhao, Gang</creator><creator>Liu, Zhiwei</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>7T5</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>2016</creationdate><title>The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma</title><author>Wang, Dadong ; Tan, Jingwang ; Xu, Yong ; Han, Mingming ; Tu, Yuliang ; Zhu, Ziman ; Dou, Chunqing ; Xin, Jin ; Tan, Xianglong ; Zeng, Jian-ping ; Zhao, Gang ; Liu, Zhiwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-11e167368e9ae7e2235fcff6fd525e8c0a39357d65d59761e6af93002743d3a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma in Situ - genetics</topic><topic>Adenocarcinoma in Situ - metabolism</topic><topic>Adenocarcinoma in Situ - pathology</topic><topic>Aged</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - metabolism</topic><topic>Carcinoma, Pancreatic Ductal - pathology</topic><topic>Case-Control Studies</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Female</topic><topic>Frizzled Receptors - genetics</topic><topic>Frizzled Receptors - metabolism</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Male</topic><topic>Membranes</topic><topic>Middle Aged</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Oncogene Proteins - genetics</topic><topic>Oncogene Proteins - metabolism</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Proteins</topic><topic>Research Article</topic><topic>Tissues</topic><topic>Ubiquitin-Protein Ligases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Dadong</creatorcontrib><creatorcontrib>Tan, Jingwang</creatorcontrib><creatorcontrib>Xu, Yong</creatorcontrib><creatorcontrib>Han, Mingming</creatorcontrib><creatorcontrib>Tu, Yuliang</creatorcontrib><creatorcontrib>Zhu, Ziman</creatorcontrib><creatorcontrib>Dou, Chunqing</creatorcontrib><creatorcontrib>Xin, Jin</creatorcontrib><creatorcontrib>Tan, Xianglong</creatorcontrib><creatorcontrib>Zeng, Jian-ping</creatorcontrib><creatorcontrib>Zhao, Gang</creatorcontrib><creatorcontrib>Liu, Zhiwei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Dadong</au><au>Tan, Jingwang</au><au>Xu, Yong</au><au>Han, Mingming</au><au>Tu, Yuliang</au><au>Zhu, Ziman</au><au>Dou, Chunqing</au><au>Xin, Jin</au><au>Tan, Xianglong</au><au>Zeng, Jian-ping</au><au>Zhao, Gang</au><au>Liu, Zhiwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2016</date><risdate>2016</risdate><volume>37</volume><issue>1</issue><spage>627</spage><epage>631</epage><pages>627-631</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><abstract>RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26240024</pmid><doi>10.1007/s13277-015-3499-7</doi><tpages>5</tpages></addata></record> |
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| subjects | Adenocarcinoma in Situ - genetics Adenocarcinoma in Situ - metabolism Adenocarcinoma in Situ - pathology Aged Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - metabolism Carcinoma, Pancreatic Ductal - pathology Case-Control Studies Cell Line, Tumor Cell Membrane - metabolism DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Female Frizzled Receptors - genetics Frizzled Receptors - metabolism Gene Expression Humans Male Membranes Middle Aged Neoplasm Grading Neoplasm Staging Oncogene Proteins - genetics Oncogene Proteins - metabolism Pancreatic cancer Pancreatic Neoplasms Pancreatic Neoplasms - genetics Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - pathology Proteins Research Article Tissues Ubiquitin-Protein Ligases |
| title | The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma |
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