The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo
Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdi...
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| Veröffentlicht in: | Oncotarget 2016-10, Vol.7 (40), p.65137-65146 |
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| creator | Kong, Sun-Young Kim, Kwang-Soo Kim, Jiewan Kim, Min Kyeong Lee, Ki Hong Lee, Je-Yong Oh, Nuri Park, Ji-In Park, Ji-Hoon Heo, Sun-Hee Shim, Sung Han Lee, Dong Ryul Kim, Keun Pil Park, Kyung-Soon |
| description | Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells. |
| doi_str_mv | 10.18632/oncotarget.11427 |
| format | Article |
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Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.11427</identifier><identifier>PMID: 27556500</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Cell Line, Tumor ; Cell Movement - physiology ; Cell Transdifferentiation - physiology ; Female ; GATA3 Transcription Factor - metabolism ; Heterografts ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Invasiveness - pathology ; Proto-Oncogene Proteins - metabolism ; Research Paper ; Transcription Factors - metabolism ; Triple Negative Breast Neoplasms - metabolism ; Triple Negative Breast Neoplasms - pathology</subject><ispartof>Oncotarget, 2016-10, Vol.7 (40), p.65137-65146</ispartof><rights>Copyright: © 2016 Kong et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-114d2cb956d1b2d6b078fb4d574edcd02cc17351233ec46a6ca76f496d0e24a53</citedby><cites>FETCH-LOGICAL-c426t-114d2cb956d1b2d6b078fb4d574edcd02cc17351233ec46a6ca76f496d0e24a53</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/PMC5323143/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323143/$$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/27556500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kong, Sun-Young</creatorcontrib><creatorcontrib>Kim, Kwang-Soo</creatorcontrib><creatorcontrib>Kim, Jiewan</creatorcontrib><creatorcontrib>Kim, Min Kyeong</creatorcontrib><creatorcontrib>Lee, Ki Hong</creatorcontrib><creatorcontrib>Lee, Je-Yong</creatorcontrib><creatorcontrib>Oh, Nuri</creatorcontrib><creatorcontrib>Park, Ji-In</creatorcontrib><creatorcontrib>Park, Ji-Hoon</creatorcontrib><creatorcontrib>Heo, Sun-Hee</creatorcontrib><creatorcontrib>Shim, Sung Han</creatorcontrib><creatorcontrib>Lee, Dong Ryul</creatorcontrib><creatorcontrib>Kim, Keun Pil</creatorcontrib><creatorcontrib>Park, Kyung-Soon</creatorcontrib><title>The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. 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These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.</description><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - physiology</subject><subject>Cell Transdifferentiation - physiology</subject><subject>Female</subject><subject>GATA3 Transcription Factor - metabolism</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Research Paper</subject><subject>Transcription Factors - metabolism</subject><subject>Triple Negative Breast Neoplasms - metabolism</subject><subject>Triple Negative Breast Neoplasms - pathology</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1PAjEUbIxGCPIDvJgevSz2e3cvJoQgGkm84Lnptl1Yw26xXTb67y0fIjYvaV86M33TAeAWoxHOBCUPrtGuVX5p2xHGjKQXoI9zlieEc3p5du6BYQgfKC7O0ozk16BHUs4FR6gPzGJl4XT-SpPZeDGmUH1VATqvVza0XrU2wKrpVKhcA1VjYG1bFWLtQCUsvI0d1KrR1kNt1-sdHHZV690evm86dwOuSrUOdnjcB-D9abqYPCfzt9nLZDxPNCOiTaILQ3SRc2FwQYwoUJqVBTM8ZdZog4jWOKUcE0qtZkIJrVJRslwYZAlTnA7A40F3sy3qSLFN9LCWG1_Vyn9Lpyr5_6apVnLpOskpoZjRKHB_FPDucxu_QNZV2PlSjXXbIHHGWYYIT7MIxQeo9i4Eb8vTMxjJfUDyLyC5Dyhy7s7nOzF-46A_dd-P6Q</recordid><startdate>20161004</startdate><enddate>20161004</enddate><creator>Kong, Sun-Young</creator><creator>Kim, Kwang-Soo</creator><creator>Kim, Jiewan</creator><creator>Kim, Min Kyeong</creator><creator>Lee, Ki Hong</creator><creator>Lee, Je-Yong</creator><creator>Oh, Nuri</creator><creator>Park, Ji-In</creator><creator>Park, Ji-Hoon</creator><creator>Heo, Sun-Hee</creator><creator>Shim, Sung Han</creator><creator>Lee, Dong Ryul</creator><creator>Kim, Keun Pil</creator><creator>Park, Kyung-Soon</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>20161004</creationdate><title>The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo</title><author>Kong, Sun-Young ; Kim, Kwang-Soo ; Kim, Jiewan ; Kim, Min Kyeong ; Lee, Ki Hong ; Lee, Je-Yong ; Oh, Nuri ; Park, Ji-In ; Park, Ji-Hoon ; Heo, Sun-Hee ; Shim, Sung Han ; Lee, Dong Ryul ; Kim, Keun Pil ; Park, Kyung-Soon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-114d2cb956d1b2d6b078fb4d574edcd02cc17351233ec46a6ca76f496d0e24a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - physiology</topic><topic>Cell Transdifferentiation - physiology</topic><topic>Female</topic><topic>GATA3 Transcription Factor - metabolism</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Research Paper</topic><topic>Transcription Factors - metabolism</topic><topic>Triple Negative Breast Neoplasms - metabolism</topic><topic>Triple Negative Breast Neoplasms - pathology</topic><toplevel>online_resources</toplevel><creatorcontrib>Kong, Sun-Young</creatorcontrib><creatorcontrib>Kim, Kwang-Soo</creatorcontrib><creatorcontrib>Kim, Jiewan</creatorcontrib><creatorcontrib>Kim, Min Kyeong</creatorcontrib><creatorcontrib>Lee, Ki Hong</creatorcontrib><creatorcontrib>Lee, Je-Yong</creatorcontrib><creatorcontrib>Oh, Nuri</creatorcontrib><creatorcontrib>Park, Ji-In</creatorcontrib><creatorcontrib>Park, Ji-Hoon</creatorcontrib><creatorcontrib>Heo, Sun-Hee</creatorcontrib><creatorcontrib>Shim, Sung Han</creatorcontrib><creatorcontrib>Lee, Dong Ryul</creatorcontrib><creatorcontrib>Kim, Keun Pil</creatorcontrib><creatorcontrib>Park, Kyung-Soon</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>Kong, Sun-Young</au><au>Kim, Kwang-Soo</au><au>Kim, Jiewan</au><au>Kim, Min Kyeong</au><au>Lee, Ki Hong</au><au>Lee, Je-Yong</au><au>Oh, Nuri</au><au>Park, Ji-In</au><au>Park, Ji-Hoon</au><au>Heo, Sun-Hee</au><au>Shim, Sung Han</au><au>Lee, Dong Ryul</au><au>Kim, Keun Pil</au><au>Park, Kyung-Soon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-10-04</date><risdate>2016</risdate><volume>7</volume><issue>40</issue><spage>65137</spage><epage>65146</epage><pages>65137-65146</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27556500</pmid><doi>10.18632/oncotarget.11427</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cell Line, Tumor Cell Movement - physiology Cell Transdifferentiation - physiology Female GATA3 Transcription Factor - metabolism Heterografts Humans Mice Mice, Inbred NOD Mice, SCID Neoplasm Invasiveness - pathology Proto-Oncogene Proteins - metabolism Research Paper Transcription Factors - metabolism Triple Negative Breast Neoplasms - metabolism Triple Negative Breast Neoplasms - pathology |
| title | The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo |
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