LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF...
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| Veröffentlicht in: | Oncotarget 2017-01, Vol.8 (2), p.3259-3273 |
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| creator | Dräger, Julia Simon-Keller, Katja Pukrop, Tobias Klemm, Florian Wilting, Jörg Sticht, Carsten Dittmann, Kai Schulz, Matthias Leuschner, Ivo Marx, Alexander Hahn, Heidi |
| description | Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness especially of ARMS cells. LEF1 knockdown experiments in cell lines reveal that depending on the cellular context, LEF1 can induce pro-apoptotic signals. LEF1 can also suppress proliferation, migration and invasiveness of RMS cells both in vitro and in vivo. Furthermore, LEF1 can induce myodifferentiation of the tumor cells. This may involve regulation of other LEF1/TCF factors i.e. TCF1, whereas β-catenin activity plays a subordinate role. Together these data suggest that LEF1 rather has tumor suppressive functions and attenuates aggressiveness in a subset of RMS. |
| doi_str_mv | 10.18632/oncotarget.13887 |
| format | Article |
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The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness especially of ARMS cells. LEF1 knockdown experiments in cell lines reveal that depending on the cellular context, LEF1 can induce pro-apoptotic signals. LEF1 can also suppress proliferation, migration and invasiveness of RMS cells both in vitro and in vivo. Furthermore, LEF1 can induce myodifferentiation of the tumor cells. This may involve regulation of other LEF1/TCF factors i.e. TCF1, whereas β-catenin activity plays a subordinate role. Together these data suggest that LEF1 rather has tumor suppressive functions and attenuates aggressiveness in a subset of RMS.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.13887</identifier><identifier>PMID: 27965462</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Apoptosis - genetics ; Biomarkers, Tumor ; Biopsy ; Cell Differentiation - genetics ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation ; Disease Progression ; Gene Expression ; Gene Knockdown Techniques ; Humans ; Lymphoid Enhancer-Binding Factor 1 - genetics ; Lymphoid Enhancer-Binding Factor 1 - metabolism ; Neoplasm Grading ; Research Paper ; Rhabdomyosarcoma - genetics ; Rhabdomyosarcoma - metabolism ; Rhabdomyosarcoma - pathology ; Tissue Array Analysis ; Wnt Signaling Pathway</subject><ispartof>Oncotarget, 2017-01, Vol.8 (2), p.3259-3273</ispartof><rights>Copyright: © 2017 Dräger et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-61845f574b78ec90cb9901bb9cbfb25ad573091bea2a59108d121df77ba180a03</citedby><cites>FETCH-LOGICAL-c356t-61845f574b78ec90cb9901bb9cbfb25ad573091bea2a59108d121df77ba180a03</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/PMC5356880/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356880/$$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/27965462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dräger, Julia</creatorcontrib><creatorcontrib>Simon-Keller, Katja</creatorcontrib><creatorcontrib>Pukrop, Tobias</creatorcontrib><creatorcontrib>Klemm, Florian</creatorcontrib><creatorcontrib>Wilting, Jörg</creatorcontrib><creatorcontrib>Sticht, Carsten</creatorcontrib><creatorcontrib>Dittmann, Kai</creatorcontrib><creatorcontrib>Schulz, Matthias</creatorcontrib><creatorcontrib>Leuschner, Ivo</creatorcontrib><creatorcontrib>Marx, Alexander</creatorcontrib><creatorcontrib>Hahn, Heidi</creatorcontrib><title>LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness especially of ARMS cells. LEF1 knockdown experiments in cell lines reveal that depending on the cellular context, LEF1 can induce pro-apoptotic signals. LEF1 can also suppress proliferation, migration and invasiveness of RMS cells both in vitro and in vivo. Furthermore, LEF1 can induce myodifferentiation of the tumor cells. This may involve regulation of other LEF1/TCF factors i.e. TCF1, whereas β-catenin activity plays a subordinate role. Together these data suggest that LEF1 rather has tumor suppressive functions and attenuates aggressiveness in a subset of RMS.</description><subject>Apoptosis - genetics</subject><subject>Biomarkers, Tumor</subject><subject>Biopsy</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation</subject><subject>Disease Progression</subject><subject>Gene Expression</subject><subject>Gene Knockdown Techniques</subject><subject>Humans</subject><subject>Lymphoid Enhancer-Binding Factor 1 - genetics</subject><subject>Lymphoid Enhancer-Binding Factor 1 - metabolism</subject><subject>Neoplasm Grading</subject><subject>Research Paper</subject><subject>Rhabdomyosarcoma - genetics</subject><subject>Rhabdomyosarcoma - metabolism</subject><subject>Rhabdomyosarcoma - pathology</subject><subject>Tissue Array Analysis</subject><subject>Wnt Signaling Pathway</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>eNpVUU1LAzEUDKLYUvsDvEiOXrYm2c0muQhSWhUKXvQoIV_bRrqbmuwK_fduP9T6Lu_BzJsZGACuMZpgXubkLjQmtCouXTvBOefsDAyxKERGKM3PT-4BGKf0gfqhBeNEXIIBYaKkRUmG4H0xm2MYne2MS7Dt6hDhJoZldCn50EDVWOibA1pvg_VV5aJrWq_aHex7BkydTq6FoYJxpbQNPS-paEKtrsBFpdbJjY97BN7ms9fpU7Z4eXyePiwyk9OyzUrMC1pRVmjGnRHIaCEQ1loYXWlClaUsRwJrp4iiAiNuMcG2YkwrzJFC-QjcH3Q3na6dNX3AqNZyE32t4lYG5eV_pPEruQxfkvb-nO8Ebo8CMXx2LrWy9sm49Vo1LnRJYk5JyUrGaE_FB6qJIaXoql8bjOS-GfnXjNw30__cnOb7_fjpIf8GvTaPXA</recordid><startdate>20170110</startdate><enddate>20170110</enddate><creator>Dräger, Julia</creator><creator>Simon-Keller, Katja</creator><creator>Pukrop, Tobias</creator><creator>Klemm, Florian</creator><creator>Wilting, Jörg</creator><creator>Sticht, Carsten</creator><creator>Dittmann, Kai</creator><creator>Schulz, Matthias</creator><creator>Leuschner, Ivo</creator><creator>Marx, Alexander</creator><creator>Hahn, Heidi</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>20170110</creationdate><title>LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma</title><author>Dräger, Julia ; Simon-Keller, Katja ; Pukrop, Tobias ; Klemm, Florian ; Wilting, Jörg ; Sticht, Carsten ; Dittmann, Kai ; Schulz, Matthias ; Leuschner, Ivo ; Marx, Alexander ; Hahn, Heidi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-61845f574b78ec90cb9901bb9cbfb25ad573091bea2a59108d121df77ba180a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Apoptosis - genetics</topic><topic>Biomarkers, Tumor</topic><topic>Biopsy</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation</topic><topic>Disease Progression</topic><topic>Gene Expression</topic><topic>Gene Knockdown Techniques</topic><topic>Humans</topic><topic>Lymphoid Enhancer-Binding Factor 1 - genetics</topic><topic>Lymphoid Enhancer-Binding Factor 1 - metabolism</topic><topic>Neoplasm Grading</topic><topic>Research Paper</topic><topic>Rhabdomyosarcoma - genetics</topic><topic>Rhabdomyosarcoma - metabolism</topic><topic>Rhabdomyosarcoma - pathology</topic><topic>Tissue Array Analysis</topic><topic>Wnt Signaling Pathway</topic><toplevel>online_resources</toplevel><creatorcontrib>Dräger, Julia</creatorcontrib><creatorcontrib>Simon-Keller, Katja</creatorcontrib><creatorcontrib>Pukrop, Tobias</creatorcontrib><creatorcontrib>Klemm, Florian</creatorcontrib><creatorcontrib>Wilting, Jörg</creatorcontrib><creatorcontrib>Sticht, Carsten</creatorcontrib><creatorcontrib>Dittmann, Kai</creatorcontrib><creatorcontrib>Schulz, Matthias</creatorcontrib><creatorcontrib>Leuschner, Ivo</creatorcontrib><creatorcontrib>Marx, Alexander</creatorcontrib><creatorcontrib>Hahn, Heidi</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>Dräger, Julia</au><au>Simon-Keller, Katja</au><au>Pukrop, Tobias</au><au>Klemm, Florian</au><au>Wilting, Jörg</au><au>Sticht, Carsten</au><au>Dittmann, Kai</au><au>Schulz, Matthias</au><au>Leuschner, Ivo</au><au>Marx, Alexander</au><au>Hahn, Heidi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-01-10</date><risdate>2017</risdate><volume>8</volume><issue>2</issue><spage>3259</spage><epage>3273</epage><pages>3259-3273</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and show characteristics of skeletal muscle differentiation. The two major RMS subtypes in children are alveolar (ARMS) and embryonal RMS (ERMS). We demonstrate that approximately 50% of ARMS and ERMS overexpress the LEF1/TCF transcription factor LEF1 when compared to normal skeletal muscle and that LEF1 can restrain aggressiveness especially of ARMS cells. LEF1 knockdown experiments in cell lines reveal that depending on the cellular context, LEF1 can induce pro-apoptotic signals. LEF1 can also suppress proliferation, migration and invasiveness of RMS cells both in vitro and in vivo. Furthermore, LEF1 can induce myodifferentiation of the tumor cells. This may involve regulation of other LEF1/TCF factors i.e. TCF1, whereas β-catenin activity plays a subordinate role. 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| subjects | Apoptosis - genetics Biomarkers, Tumor Biopsy Cell Differentiation - genetics Cell Line, Tumor Cell Movement - genetics Cell Proliferation Disease Progression Gene Expression Gene Knockdown Techniques Humans Lymphoid Enhancer-Binding Factor 1 - genetics Lymphoid Enhancer-Binding Factor 1 - metabolism Neoplasm Grading Research Paper Rhabdomyosarcoma - genetics Rhabdomyosarcoma - metabolism Rhabdomyosarcoma - pathology Tissue Array Analysis Wnt Signaling Pathway |
| title | LEF1 reduces tumor progression and induces myodifferentiation in a subset of rhabdomyosarcoma |
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