Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells
Expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), which correlates with tumor invasion and metastasis, has been known to be regulated by several intracellular signaling pathways. Since the CD9 membrane protein has been implicated in signal transduction and malignant progression of c...
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| Veröffentlicht in: | Experimental & molecular medicine 2005-06, Vol.37 (3), p.230-239 |
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| creator | Hong, In-Kee Kim, Young-Myeong Jeoung, Doo-Il Kim, Keun-Cheol Lee, Hansoo |
| description | Expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), which correlates with tumor invasion and metastasis, has been known to be regulated by several intracellular signaling pathways. Since the CD9 membrane protein has been implicated in signal transduction and malignant progression of cancer cells, we examined the functional involvement of CD9 in the regulation of MMP-2 and MMP-9 expression by using stable CD9 transfectant clones of MelJuso human melanoma cells. The CD9 cDNA-transfected cells with elevated CD9 expression displayed increased MMP-2 and decreased MMP-9 expression when compared with the mock transfectant cells. Among several signal pathway inhibitors tested, SB203580 and SP600125, which inhibit p38 MAPK and JNK respectively, completely blocked the CD9-stimulated MMP-2 expression. Phosphorylation levels of p38 MAPK and c-Jun in MelJuso cells were also significantly increased by CD9 transfection. In addition, the down-regulation of p38 MAPK and JNK by siRNA transfection resulted in a decrease in MMP-2 expression by MelJuso cells. Promoter analysis and gel shift assay showed that the CD9-induced MMP-2 expression is mediated by a functional AP-1 site through interactions with AP-1 transcription factors including c-Jun. These results suggest that CD9 induces MMP-2 expression by activating c- Jun through p38 MAPK and JNK signaling pathways in human melanoma cells. |
| doi_str_mv | 10.1038/emm.2005.31 |
| format | Article |
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Since the CD9 membrane protein has been implicated in signal transduction and malignant progression of cancer cells, we examined the functional involvement of CD9 in the regulation of MMP-2 and MMP-9 expression by using stable CD9 transfectant clones of MelJuso human melanoma cells. The CD9 cDNA-transfected cells with elevated CD9 expression displayed increased MMP-2 and decreased MMP-9 expression when compared with the mock transfectant cells. Among several signal pathway inhibitors tested, SB203580 and SP600125, which inhibit p38 MAPK and JNK respectively, completely blocked the CD9-stimulated MMP-2 expression. Phosphorylation levels of p38 MAPK and c-Jun in MelJuso cells were also significantly increased by CD9 transfection. In addition, the down-regulation of p38 MAPK and JNK by siRNA transfection resulted in a decrease in MMP-2 expression by MelJuso cells. Promoter analysis and gel shift assay showed that the CD9-induced MMP-2 expression is mediated by a functional AP-1 site through interactions with AP-1 transcription factors including c-Jun. These results suggest that CD9 induces MMP-2 expression by activating c- Jun through p38 MAPK and JNK signaling pathways in human melanoma cells.</description><identifier>ISSN: 1226-3613</identifier><identifier>ISSN: 2092-6413</identifier><identifier>EISSN: 2092-6413</identifier><identifier>DOI: 10.1038/emm.2005.31</identifier><identifier>PMID: 16000878</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>Antigens, CD - metabolism ; Electrophoretic Mobility Shift Assay ; Enzyme Activation ; Humans ; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases - genetics ; JNK Mitogen-Activated Protein Kinases - metabolism ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Melanoma - metabolism ; Melanoma - pathology ; Membrane Glycoproteins - metabolism ; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases - genetics ; p38 Mitogen-Activated Protein Kinases - metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-jun - metabolism ; RNA, Small Interfering - pharmacology ; Signal Transduction ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Tetraspanin-29 ; Transcription Factor AP-1 - metabolism ; Transfection</subject><ispartof>Experimental & molecular medicine, 2005-06, Vol.37 (3), p.230-239</ispartof><rights>Copyright Nature Publishing Group Jun 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-7f50e8bcb15bc3bf0dcca3daa266362f72b87f3d23b9c0e3cfd94c8c63aa7eb43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16000878$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hong, In-Kee</creatorcontrib><creatorcontrib>Kim, Young-Myeong</creatorcontrib><creatorcontrib>Jeoung, Doo-Il</creatorcontrib><creatorcontrib>Kim, Keun-Cheol</creatorcontrib><creatorcontrib>Lee, Hansoo</creatorcontrib><title>Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells</title><title>Experimental & molecular medicine</title><addtitle>Exp Mol Med</addtitle><description>Expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), which correlates with tumor invasion and metastasis, has been known to be regulated by several intracellular signaling pathways. Since the CD9 membrane protein has been implicated in signal transduction and malignant progression of cancer cells, we examined the functional involvement of CD9 in the regulation of MMP-2 and MMP-9 expression by using stable CD9 transfectant clones of MelJuso human melanoma cells. The CD9 cDNA-transfected cells with elevated CD9 expression displayed increased MMP-2 and decreased MMP-9 expression when compared with the mock transfectant cells. Among several signal pathway inhibitors tested, SB203580 and SP600125, which inhibit p38 MAPK and JNK respectively, completely blocked the CD9-stimulated MMP-2 expression. Phosphorylation levels of p38 MAPK and c-Jun in MelJuso cells were also significantly increased by CD9 transfection. In addition, the down-regulation of p38 MAPK and JNK by siRNA transfection resulted in a decrease in MMP-2 expression by MelJuso cells. Promoter analysis and gel shift assay showed that the CD9-induced MMP-2 expression is mediated by a functional AP-1 site through interactions with AP-1 transcription factors including c-Jun. These results suggest that CD9 induces MMP-2 expression by activating c- Jun through p38 MAPK and JNK signaling pathways in human melanoma cells.</description><subject>Antigens, CD - metabolism</subject><subject>Electrophoretic Mobility Shift Assay</subject><subject>Enzyme Activation</subject><subject>Humans</subject><subject>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>JNK Mitogen-Activated Protein Kinases - genetics</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - pathology</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>p38 Mitogen-Activated Protein Kinases - genetics</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Proto-Oncogene Proteins c-jun - metabolism</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Signal Transduction</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Tetraspanin-29</subject><subject>Transcription Factor AP-1 - metabolism</subject><subject>Transfection</subject><issn>1226-3613</issn><issn>2092-6413</issn><issn>2092-6413</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp90U9v1DAQhnELgehSeuKOLCEhpDbL2OM4zrFaoPTP0h7KORo7Dk21cdI4oey3x6uuhMShJ19-ejXWw9g7AUsBaD77rltKgHyJ4gVbSChlppXAl2whpNQZaoEH7E2M9wAyV4V6zQ6EBgBTmAXrb_00UhwotIGvvpS8DfXsfOTr9U0muf8zjD7Gtg_cbjm5qf1NUxt-8QENX5_eXJ7wix-XnELNXXYxBz7QdPdI25h2-N3cUeCd31DoO-LObzbxLXvV0Cb6o_17yH5--3q7-p5dXZ-dr06vMqdyMWVFk4M31lmRW4e2gdo5wppIao1aNoW0pmiwlmhLBx5dU5fKGaeRqPBW4SH7-LQ7jP3D7ONUdW3cXUDB93OstAEoFRQJfnoWCqM0lqgAEv3wH73v5zGkbySVAkiNMk_q-Em5sY9x9E01jG1H47YSUO2CVSlYtQtWoUj6_X5ztp2v_9l9IfwLG7mPZQ</recordid><startdate>20050630</startdate><enddate>20050630</enddate><creator>Hong, In-Kee</creator><creator>Kim, Young-Myeong</creator><creator>Jeoung, Doo-Il</creator><creator>Kim, Keun-Cheol</creator><creator>Lee, Hansoo</creator><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20050630</creationdate><title>Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells</title><author>Hong, In-Kee ; Kim, Young-Myeong ; Jeoung, Doo-Il ; Kim, Keun-Cheol ; Lee, Hansoo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-7f50e8bcb15bc3bf0dcca3daa266362f72b87f3d23b9c0e3cfd94c8c63aa7eb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Antigens, CD - 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metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Tetraspanin-29</topic><topic>Transcription Factor AP-1 - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hong, In-Kee</creatorcontrib><creatorcontrib>Kim, Young-Myeong</creatorcontrib><creatorcontrib>Jeoung, Doo-Il</creatorcontrib><creatorcontrib>Kim, Keun-Cheol</creatorcontrib><creatorcontrib>Lee, Hansoo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental & molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hong, In-Kee</au><au>Kim, Young-Myeong</au><au>Jeoung, Doo-Il</au><au>Kim, Keun-Cheol</au><au>Lee, Hansoo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells</atitle><jtitle>Experimental & molecular medicine</jtitle><addtitle>Exp Mol Med</addtitle><date>2005-06-30</date><risdate>2005</risdate><volume>37</volume><issue>3</issue><spage>230</spage><epage>239</epage><pages>230-239</pages><issn>1226-3613</issn><issn>2092-6413</issn><eissn>2092-6413</eissn><abstract>Expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), which correlates with tumor invasion and metastasis, has been known to be regulated by several intracellular signaling pathways. Since the CD9 membrane protein has been implicated in signal transduction and malignant progression of cancer cells, we examined the functional involvement of CD9 in the regulation of MMP-2 and MMP-9 expression by using stable CD9 transfectant clones of MelJuso human melanoma cells. The CD9 cDNA-transfected cells with elevated CD9 expression displayed increased MMP-2 and decreased MMP-9 expression when compared with the mock transfectant cells. Among several signal pathway inhibitors tested, SB203580 and SP600125, which inhibit p38 MAPK and JNK respectively, completely blocked the CD9-stimulated MMP-2 expression. Phosphorylation levels of p38 MAPK and c-Jun in MelJuso cells were also significantly increased by CD9 transfection. In addition, the down-regulation of p38 MAPK and JNK by siRNA transfection resulted in a decrease in MMP-2 expression by MelJuso cells. Promoter analysis and gel shift assay showed that the CD9-induced MMP-2 expression is mediated by a functional AP-1 site through interactions with AP-1 transcription factors including c-Jun. These results suggest that CD9 induces MMP-2 expression by activating c- Jun through p38 MAPK and JNK signaling pathways in human melanoma cells.</abstract><cop>United States</cop><pub>Springer Nature B.V</pub><pmid>16000878</pmid><doi>10.1038/emm.2005.31</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antigens, CD - metabolism Electrophoretic Mobility Shift Assay Enzyme Activation Humans JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors JNK Mitogen-Activated Protein Kinases - genetics JNK Mitogen-Activated Protein Kinases - metabolism Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Melanoma - metabolism Melanoma - pathology Membrane Glycoproteins - metabolism p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors p38 Mitogen-Activated Protein Kinases - genetics p38 Mitogen-Activated Protein Kinases - metabolism Promoter Regions, Genetic Proto-Oncogene Proteins c-jun - metabolism RNA, Small Interfering - pharmacology Signal Transduction Skin Neoplasms - metabolism Skin Neoplasms - pathology Tetraspanin-29 Transcription Factor AP-1 - metabolism Transfection |
| title | Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells |
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