DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer
DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC ce...
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| Veröffentlicht in: | Oncotarget 2017-02, Vol.8 (7), p.12133-12144 |
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| creator | Shen, Jiliang Zhou, Senjun Shi, Liang Liu, Xiaolong Lin, Hui Yu, Hong Xiaoliang Tang, Jiacheng Yu, Tunan Cai, Xiujun |
| description | DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway. Angiogenesis was associated with the tumor metastasis in the mouse model and was impaired by DUSP1, which suppressed VEGF expression. These results suggest that DUSP1 suppresses GBC growth and metastasis by targeting the DUSP1-pERK-MMP2/VEGF axis. Identification of the DUSP1-pERK-MMP2/VEGF signals may provide new biomarkers and/or therapeutic targets to better suppress GBC metastasis in the future. |
| doi_str_mv | 10.18632/oncotarget.14815 |
| format | Article |
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Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway. Angiogenesis was associated with the tumor metastasis in the mouse model and was impaired by DUSP1, which suppressed VEGF expression. These results suggest that DUSP1 suppresses GBC growth and metastasis by targeting the DUSP1-pERK-MMP2/VEGF axis. Identification of the DUSP1-pERK-MMP2/VEGF signals may provide new biomarkers and/or therapeutic targets to better suppress GBC metastasis in the future.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.14815</identifier><identifier>PMID: 28129656</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Blotting, Western ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; Dual Specificity Phosphatase 1 - genetics ; Dual Specificity Phosphatase 1 - metabolism ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Gallbladder Neoplasms - blood supply ; Gallbladder Neoplasms - genetics ; Gallbladder Neoplasms - metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2 ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neovascularization, Pathologic - genetics ; Research Paper ; Reverse Transcriptase Polymerase Chain Reaction ; RNA Interference ; Signal Transduction ; Transplantation, Heterologous ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Oncotarget, 2017-02, Vol.8 (7), p.12133-12144</ispartof><rights>Copyright: © 2017 Shen et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-1f7cc45391feee4f46df4f85e54878c84774cfe2e47414575283d0e201c644b33</citedby><cites>FETCH-LOGICAL-c356t-1f7cc45391feee4f46df4f85e54878c84774cfe2e47414575283d0e201c644b33</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/PMC5355331/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355331/$$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/28129656$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shen, Jiliang</creatorcontrib><creatorcontrib>Zhou, Senjun</creatorcontrib><creatorcontrib>Shi, Liang</creatorcontrib><creatorcontrib>Liu, Xiaolong</creatorcontrib><creatorcontrib>Lin, Hui</creatorcontrib><creatorcontrib>Yu, Hong</creatorcontrib><creatorcontrib>Xiaoliang</creatorcontrib><creatorcontrib>Tang, Jiacheng</creatorcontrib><creatorcontrib>Yu, Tunan</creatorcontrib><creatorcontrib>Cai, Xiujun</creatorcontrib><title>DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway. Angiogenesis was associated with the tumor metastasis in the mouse model and was impaired by DUSP1, which suppressed VEGF expression. These results suggest that DUSP1 suppresses GBC growth and metastasis by targeting the DUSP1-pERK-MMP2/VEGF axis. Identification of the DUSP1-pERK-MMP2/VEGF signals may provide new biomarkers and/or therapeutic targets to better suppress GBC metastasis in the future.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Dual Specificity Phosphatase 1 - genetics</subject><subject>Dual Specificity Phosphatase 1 - metabolism</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>Gallbladder Neoplasms - blood supply</subject><subject>Gallbladder Neoplasms - genetics</subject><subject>Gallbladder Neoplasms - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Matrix Metalloproteinase 2</subject><subject>Mice, Nude</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Research Paper</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA Interference</subject><subject>Signal Transduction</subject><subject>Transplantation, Heterologous</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1LAzEQDaJY0f4AL7JHD1Y3yWQ3exHEbxAU1HNIs5NtZJvUZCv4742tnyGQCfPem-E9QvZpeUxlxdlJ8CYMOnY4HFOQVGyQHdpAM2FC8M0_9YiMU3op8xFQS9ZskxGTlDWVqHaIvnh-fKCF8zM3dUMqDPZ9sYihdxajHlzwR8UcB53ydanQvs3Yt1wHv_po37nQocfPrvNFp_t-2uu2xVgY7Q3GPbJldZ9w_PXukuery6fzm8nd_fXt-dndxHBRDRNqa2NA8IZaRAQLVWvBSoECZC2NhLoGY5Eh1EBB1IJJ3pbISmoqgCnnu-R0rbtYTufYGvRD1L1aRDfX8V0F7dT_jncz1YU3JXg2idMscPglEMPrEtOg5i59-qE9hmVS2XVWVwwkZChdQ00MKUW0P2NoqVbpqN901CqdzDn4u98P4zsL_gEzG4_B</recordid><startdate>20170214</startdate><enddate>20170214</enddate><creator>Shen, Jiliang</creator><creator>Zhou, Senjun</creator><creator>Shi, Liang</creator><creator>Liu, Xiaolong</creator><creator>Lin, Hui</creator><creator>Yu, Hong</creator><creator>Xiaoliang</creator><creator>Tang, Jiacheng</creator><creator>Yu, Tunan</creator><creator>Cai, Xiujun</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>20170214</creationdate><title>DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer</title><author>Shen, Jiliang ; Zhou, Senjun ; Shi, Liang ; Liu, Xiaolong ; Lin, Hui ; Yu, Hong ; Xiaoliang ; Tang, Jiacheng ; Yu, Tunan ; Cai, Xiujun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-1f7cc45391feee4f46df4f85e54878c84774cfe2e47414575283d0e201c644b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Dual Specificity Phosphatase 1 - genetics</topic><topic>Dual Specificity Phosphatase 1 - metabolism</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>Gallbladder Neoplasms - blood supply</topic><topic>Gallbladder Neoplasms - genetics</topic><topic>Gallbladder Neoplasms - metabolism</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Matrix Metalloproteinase 2</topic><topic>Mice, Nude</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Metastasis</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Research Paper</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA Interference</topic><topic>Signal Transduction</topic><topic>Transplantation, Heterologous</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Shen, Jiliang</creatorcontrib><creatorcontrib>Zhou, Senjun</creatorcontrib><creatorcontrib>Shi, Liang</creatorcontrib><creatorcontrib>Liu, Xiaolong</creatorcontrib><creatorcontrib>Lin, Hui</creatorcontrib><creatorcontrib>Yu, Hong</creatorcontrib><creatorcontrib>Xiaoliang</creatorcontrib><creatorcontrib>Tang, Jiacheng</creatorcontrib><creatorcontrib>Yu, Tunan</creatorcontrib><creatorcontrib>Cai, Xiujun</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>Shen, Jiliang</au><au>Zhou, Senjun</au><au>Shi, Liang</au><au>Liu, Xiaolong</au><au>Lin, Hui</au><au>Yu, Hong</au><au>Xiaoliang</au><au>Tang, Jiacheng</au><au>Yu, Tunan</au><au>Cai, Xiujun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-02-14</date><risdate>2017</risdate><volume>8</volume><issue>7</issue><spage>12133</spage><epage>12144</epage><pages>12133-12144</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway. Angiogenesis was associated with the tumor metastasis in the mouse model and was impaired by DUSP1, which suppressed VEGF expression. These results suggest that DUSP1 suppresses GBC growth and metastasis by targeting the DUSP1-pERK-MMP2/VEGF axis. Identification of the DUSP1-pERK-MMP2/VEGF signals may provide new biomarkers and/or therapeutic targets to better suppress GBC metastasis in the future.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28129656</pmid><doi>10.18632/oncotarget.14815</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blotting, Western Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Dual Specificity Phosphatase 1 - genetics Dual Specificity Phosphatase 1 - metabolism Extracellular Signal-Regulated MAP Kinases - metabolism Female Gallbladder Neoplasms - blood supply Gallbladder Neoplasms - genetics Gallbladder Neoplasms - metabolism Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Matrix Metalloproteinase 2 Mice, Nude Neoplasm Invasiveness Neoplasm Metastasis Neovascularization, Pathologic - genetics Research Paper Reverse Transcriptase Polymerase Chain Reaction RNA Interference Signal Transduction Transplantation, Heterologous Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism |
| title | DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer |
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