Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer
The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing α1,6-fucosylation in mammals, has been observed in several malignant cancers including liver, ovarian, thyroid, and colorectal cancers. However, the pathological role and the regulatory mechanism of FUT8 in cancers remain l...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-01, Vol.110 (2), p.630-635 |
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| creator | Chen, Chien-Yu Jan, Yi-Hua Juan, Yi-Hsiu Yang, Chih-Jen Huang, Ming-Shyan Yu, Chong-Jen Yang, Pan-Chyr Hsiao, Michael Hsu, Tsui-Ling Wong, Chi-Huey |
| description | The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing α1,6-fucosylation in mammals, has been observed in several malignant cancers including liver, ovarian, thyroid, and colorectal cancers. However, the pathological role and the regulatory mechanism of FUT8 in cancers remain largely unknown. In the current study, we report that the expression of FUT8 is up-regulated in nonsmall cell lung cancer (NSCLC) and correlates with tumor metastasis, disease recurrence, and poor survival in patients with NSCLC. Knocking down FUT8 in aggressive lung cancer cell lines significantly inhibits their malignant behaviors including in vitro invasion and cell proliferation, as well as in vivo metastasis and tumor growth. The results of glycoproteomic and microarray analyses show that FUT8 globally modifies surface antigens, receptors, and adhesion molecules and is involved in the regulation of dozens of genes associated with malignancy, suggesting that FUT8 contributes to tumor progression through multiple mechanisms. Moreover, we show that FUT8 is up-regulated during epithelial–mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via the transactivation of β-catenin/lymphoid enhancer-binding factor-1 (LEF-1). These results provide a model to illustrate the relation between FUT8 expression and lung cancer progression and point to a promising direction for the prognosis and therapy of lung cancer. |
| doi_str_mv | 10.1073/pnas.1220425110 |
| format | Article |
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However, the pathological role and the regulatory mechanism of FUT8 in cancers remain largely unknown. In the current study, we report that the expression of FUT8 is up-regulated in nonsmall cell lung cancer (NSCLC) and correlates with tumor metastasis, disease recurrence, and poor survival in patients with NSCLC. Knocking down FUT8 in aggressive lung cancer cell lines significantly inhibits their malignant behaviors including in vitro invasion and cell proliferation, as well as in vivo metastasis and tumor growth. The results of glycoproteomic and microarray analyses show that FUT8 globally modifies surface antigens, receptors, and adhesion molecules and is involved in the regulation of dozens of genes associated with malignancy, suggesting that FUT8 contributes to tumor progression through multiple mechanisms. Moreover, we show that FUT8 is up-regulated during epithelial–mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via the transactivation of β-catenin/lymphoid enhancer-binding factor-1 (LEF-1). These results provide a model to illustrate the relation between FUT8 expression and lung cancer progression and point to a promising direction for the prognosis and therapy of lung cancer.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1220425110</identifier><identifier>PMID: 23267084</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>adhesion ; animal ovaries ; Animals ; beta Catenin - metabolism ; Biological Sciences ; Cadherins ; Cancer ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Cell adhesion & migration ; Cell growth ; Cell Line, Tumor ; Cell lines ; Cell Proliferation ; colorectal neoplasms ; Enzymes ; Epithelial cells ; Epithelial-Mesenchymal Transition - physiology ; Female ; Fucosyltransferases - genetics ; Fucosyltransferases - metabolism ; Gene Expression Regulation, Neoplastic - genetics ; Gene Expression Regulation, Neoplastic - physiology ; Gene Knockdown Techniques ; genes ; Humans ; liver ; Lung - metabolism ; Lung - pathology ; Lung cancer ; Lung neoplasms ; Lungs ; Lymphoid Enhancer-Binding Factor 1 - metabolism ; mammals ; Metastasis ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Microarray Analysis ; microarray technology ; Models, Biological ; Neoplasm Invasiveness - physiopathology ; Neoplasm Metastasis - physiopathology ; patients ; prognosis ; receptors ; relapse ; surface antigens ; Survival analysis ; therapeutics ; transcriptional activation ; Transplantation, Heterologous ; Tumors ; Up regulation</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-01, Vol.110 (2), p.630-635</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jan 8, 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-b307f51d350535ef804124d1a3a904e5a9be7d460413218cb93ed070d7158fb73</citedby><cites>FETCH-LOGICAL-c588t-b307f51d350535ef804124d1a3a904e5a9be7d460413218cb93ed070d7158fb73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/2.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/42553841$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/42553841$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23267084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Chien-Yu</creatorcontrib><creatorcontrib>Jan, Yi-Hua</creatorcontrib><creatorcontrib>Juan, Yi-Hsiu</creatorcontrib><creatorcontrib>Yang, Chih-Jen</creatorcontrib><creatorcontrib>Huang, Ming-Shyan</creatorcontrib><creatorcontrib>Yu, Chong-Jen</creatorcontrib><creatorcontrib>Yang, Pan-Chyr</creatorcontrib><creatorcontrib>Hsiao, Michael</creatorcontrib><creatorcontrib>Hsu, Tsui-Ling</creatorcontrib><creatorcontrib>Wong, Chi-Huey</creatorcontrib><title>Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing α1,6-fucosylation in mammals, has been observed in several malignant cancers including liver, ovarian, thyroid, and colorectal cancers. However, the pathological role and the regulatory mechanism of FUT8 in cancers remain largely unknown. In the current study, we report that the expression of FUT8 is up-regulated in nonsmall cell lung cancer (NSCLC) and correlates with tumor metastasis, disease recurrence, and poor survival in patients with NSCLC. Knocking down FUT8 in aggressive lung cancer cell lines significantly inhibits their malignant behaviors including in vitro invasion and cell proliferation, as well as in vivo metastasis and tumor growth. The results of glycoproteomic and microarray analyses show that FUT8 globally modifies surface antigens, receptors, and adhesion molecules and is involved in the regulation of dozens of genes associated with malignancy, suggesting that FUT8 contributes to tumor progression through multiple mechanisms. Moreover, we show that FUT8 is up-regulated during epithelial–mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via the transactivation of β-catenin/lymphoid enhancer-binding factor-1 (LEF-1). These results provide a model to illustrate the relation between FUT8 expression and lung cancer progression and point to a promising direction for the prognosis and therapy of lung cancer.</description><subject>adhesion</subject><subject>animal ovaries</subject><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Biological Sciences</subject><subject>Cadherins</subject><subject>Cancer</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cell Proliferation</subject><subject>colorectal neoplasms</subject><subject>Enzymes</subject><subject>Epithelial cells</subject><subject>Epithelial-Mesenchymal Transition - physiology</subject><subject>Female</subject><subject>Fucosyltransferases - genetics</subject><subject>Fucosyltransferases - metabolism</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Gene Knockdown Techniques</subject><subject>genes</subject><subject>Humans</subject><subject>liver</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lung cancer</subject><subject>Lung neoplasms</subject><subject>Lungs</subject><subject>Lymphoid Enhancer-Binding Factor 1 - metabolism</subject><subject>mammals</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Microarray Analysis</subject><subject>microarray technology</subject><subject>Models, Biological</subject><subject>Neoplasm Invasiveness - physiopathology</subject><subject>Neoplasm Metastasis - physiopathology</subject><subject>patients</subject><subject>prognosis</subject><subject>receptors</subject><subject>relapse</subject><subject>surface antigens</subject><subject>Survival analysis</subject><subject>therapeutics</subject><subject>transcriptional activation</subject><subject>Transplantation, Heterologous</subject><subject>Tumors</subject><subject>Up regulation</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EotuFMyfAEhcuaWf8ETsXJFTRgqjEAXq2HMdZssrai50g9b_H0S5b4MLFI_n95mlmHiEvEC4QFL_cB5svkDEQTCLCI7JCaLCqRQOPyQqAqUoLJs7Iec5bAGikhqfkjHFWK9BiRT5fzy7m-3FKNuTeJ5s91dRmamk_BzcNMdiRJr-ZRzvFRGNPQwx5Z8eROl-ecQ4b6mxwPj0jT3o7Zv_8WNfk7vrDt6uP1e2Xm09X728rJ7WeqpaD6iV2XILk0vcaBDLRoeW2AeGlbVqvOlGXb85Qu7bhvgMFnUKp-1bxNXl38N3P7c53zocy_Wj2adjZdG-iHczfShi-m038abgUUildDN4eDVL8Mfs8md2Ql21s8HHOBjVwhFqI5v8oU5xL1ihW0Df_oNs4p3K-haq1BKGxLtTlgXIp5px8f5obwSyZmiVT85Bp6Xj157on_neIBXh5BJbOk13xY6bm8KBvc4nwBBR7yXU58pq8Pui9jcZu0pDN3VcGWAMg17ys9gssz7h1</recordid><startdate>20130108</startdate><enddate>20130108</enddate><creator>Chen, Chien-Yu</creator><creator>Jan, Yi-Hua</creator><creator>Juan, Yi-Hsiu</creator><creator>Yang, Chih-Jen</creator><creator>Huang, Ming-Shyan</creator><creator>Yu, Chong-Jen</creator><creator>Yang, Pan-Chyr</creator><creator>Hsiao, Michael</creator><creator>Hsu, Tsui-Ling</creator><creator>Wong, Chi-Huey</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20130108</creationdate><title>Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer</title><author>Chen, Chien-Yu ; Jan, Yi-Hua ; Juan, Yi-Hsiu ; Yang, Chih-Jen ; Huang, Ming-Shyan ; Yu, Chong-Jen ; Yang, Pan-Chyr ; Hsiao, Michael ; Hsu, Tsui-Ling ; Wong, Chi-Huey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c588t-b307f51d350535ef804124d1a3a904e5a9be7d460413218cb93ed070d7158fb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>adhesion</topic><topic>animal ovaries</topic><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>Biological Sciences</topic><topic>Cadherins</topic><topic>Cancer</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Cell adhesion & migration</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cell Proliferation</topic><topic>colorectal neoplasms</topic><topic>Enzymes</topic><topic>Epithelial cells</topic><topic>Epithelial-Mesenchymal Transition - physiology</topic><topic>Female</topic><topic>Fucosyltransferases - genetics</topic><topic>Fucosyltransferases - metabolism</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Gene Knockdown Techniques</topic><topic>genes</topic><topic>Humans</topic><topic>liver</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Lung cancer</topic><topic>Lung neoplasms</topic><topic>Lungs</topic><topic>Lymphoid Enhancer-Binding Factor 1 - metabolism</topic><topic>mammals</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Microarray Analysis</topic><topic>microarray technology</topic><topic>Models, Biological</topic><topic>Neoplasm Invasiveness - physiopathology</topic><topic>Neoplasm Metastasis - physiopathology</topic><topic>patients</topic><topic>prognosis</topic><topic>receptors</topic><topic>relapse</topic><topic>surface antigens</topic><topic>Survival analysis</topic><topic>therapeutics</topic><topic>transcriptional activation</topic><topic>Transplantation, Heterologous</topic><topic>Tumors</topic><topic>Up regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Chien-Yu</creatorcontrib><creatorcontrib>Jan, Yi-Hua</creatorcontrib><creatorcontrib>Juan, Yi-Hsiu</creatorcontrib><creatorcontrib>Yang, Chih-Jen</creatorcontrib><creatorcontrib>Huang, Ming-Shyan</creatorcontrib><creatorcontrib>Yu, Chong-Jen</creatorcontrib><creatorcontrib>Yang, Pan-Chyr</creatorcontrib><creatorcontrib>Hsiao, Michael</creatorcontrib><creatorcontrib>Hsu, Tsui-Ling</creatorcontrib><creatorcontrib>Wong, Chi-Huey</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Chien-Yu</au><au>Jan, Yi-Hua</au><au>Juan, Yi-Hsiu</au><au>Yang, Chih-Jen</au><au>Huang, Ming-Shyan</au><au>Yu, Chong-Jen</au><au>Yang, Pan-Chyr</au><au>Hsiao, Michael</au><au>Hsu, Tsui-Ling</au><au>Wong, Chi-Huey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-01-08</date><risdate>2013</risdate><volume>110</volume><issue>2</issue><spage>630</spage><epage>635</epage><pages>630-635</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing α1,6-fucosylation in mammals, has been observed in several malignant cancers including liver, ovarian, thyroid, and colorectal cancers. However, the pathological role and the regulatory mechanism of FUT8 in cancers remain largely unknown. In the current study, we report that the expression of FUT8 is up-regulated in nonsmall cell lung cancer (NSCLC) and correlates with tumor metastasis, disease recurrence, and poor survival in patients with NSCLC. Knocking down FUT8 in aggressive lung cancer cell lines significantly inhibits their malignant behaviors including in vitro invasion and cell proliferation, as well as in vivo metastasis and tumor growth. The results of glycoproteomic and microarray analyses show that FUT8 globally modifies surface antigens, receptors, and adhesion molecules and is involved in the regulation of dozens of genes associated with malignancy, suggesting that FUT8 contributes to tumor progression through multiple mechanisms. Moreover, we show that FUT8 is up-regulated during epithelial–mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via the transactivation of β-catenin/lymphoid enhancer-binding factor-1 (LEF-1). These results provide a model to illustrate the relation between FUT8 expression and lung cancer progression and point to a promising direction for the prognosis and therapy of lung cancer.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>23267084</pmid><doi>10.1073/pnas.1220425110</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | adhesion animal ovaries Animals beta Catenin - metabolism Biological Sciences Cadherins Cancer Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Cell adhesion & migration Cell growth Cell Line, Tumor Cell lines Cell Proliferation colorectal neoplasms Enzymes Epithelial cells Epithelial-Mesenchymal Transition - physiology Female Fucosyltransferases - genetics Fucosyltransferases - metabolism Gene Expression Regulation, Neoplastic - genetics Gene Expression Regulation, Neoplastic - physiology Gene Knockdown Techniques genes Humans liver Lung - metabolism Lung - pathology Lung cancer Lung neoplasms Lungs Lymphoid Enhancer-Binding Factor 1 - metabolism mammals Metastasis Mice Mice, Inbred NOD Mice, SCID Microarray Analysis microarray technology Models, Biological Neoplasm Invasiveness - physiopathology Neoplasm Metastasis - physiopathology patients prognosis receptors relapse surface antigens Survival analysis therapeutics transcriptional activation Transplantation, Heterologous Tumors Up regulation |
| title | Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer |
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