HOXB13 controls cell state through super-enhancers
Expression of the homeodomain transcription factor HOXB13 has been demonstrated in several malignancies but its role in tumorigenesis remains elusive. We observed high levels of HOXB13 in poorly differentiated pediatric tumors including a highly aggressive childhood neoplasm - malignant rhabdoid tum...
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| Veröffentlicht in: | Experimental cell research 2020-08, Vol.393 (1), p.112039-112039, Article 112039 |
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| container_title | Experimental cell research |
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| creator | Aspuria, Paul-Joseph Cheon, Dong-Joo Gozo, Maricel C. Beach, Jessica A. Recouvreux, Maria Sol Walts, Ann E. Karlan, Beth Y. Orsulic, Sandra |
| description | Expression of the homeodomain transcription factor HOXB13 has been demonstrated in several malignancies but its role in tumorigenesis remains elusive. We observed high levels of HOXB13 in poorly differentiated pediatric tumors including a highly aggressive childhood neoplasm - malignant rhabdoid tumor. In a xenograft model of rhabdoid tumor, knockout of HOXB13 diminished tumor growth while partial knockdown of HOXB13 promoted differentiation of tumor cells into bone. These results suggest that HOXB13 enhances rhabdoid malignancy by interfering with mesenchymal stem cell differentiation. Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. Mechanistically, we demonstrated that HOXB13 binds to super-enhancer regions regulating genes involved in differentiation and tumorigenesis.
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•HOXB13 is aberrantly overexpressed in poorly differentiated sarcomas.•Knockdown of HOXB13 in a rhabdoid tumor xenograft leads to osteogenic differentiation.•Overexpression of HOXB13 inhibits differentiation of mesenchymal progenitor cells.•HOXB13 is a master transcription factor that regulates genes involved in cell state. |
| doi_str_mv | 10.1016/j.yexcr.2020.112039 |
| format | Article |
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[Display omitted]
•HOXB13 is aberrantly overexpressed in poorly differentiated sarcomas.•Knockdown of HOXB13 in a rhabdoid tumor xenograft leads to osteogenic differentiation.•Overexpression of HOXB13 inhibits differentiation of mesenchymal progenitor cells.•HOXB13 is a master transcription factor that regulates genes involved in cell state.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1016/j.yexcr.2020.112039</identifier><identifier>PMID: 32376288</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adipogenesis ; Bone and Bones - metabolism ; Cell Differentiation - genetics ; Cell Differentiation - physiology ; Differentiation ; Gene Expression Regulation - genetics ; Genes, Homeobox - genetics ; Homeobox ; Homeodomain Proteins - metabolism ; HOXB13 ; Humans ; Mesenchymal stem cells ; Mesenchymal Stem Cells - cytology ; Myogenesis ; Osteogenesis ; Osteogenesis - physiology ; Rhabdoid tumor ; Sarcoma ; Super-enhancer ; Transcription Factors - metabolism</subject><ispartof>Experimental cell research, 2020-08, Vol.393 (1), p.112039-112039, Article 112039</ispartof><rights>2020 The Author(s)</rights><rights>Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-f4e63a173d691e54a8cc6866f335a461e57455c6ecbc294caf06f07a87a564d03</citedby><cites>FETCH-LOGICAL-c359t-f4e63a173d691e54a8cc6866f335a461e57455c6ecbc294caf06f07a87a564d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.yexcr.2020.112039$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32376288$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aspuria, Paul-Joseph</creatorcontrib><creatorcontrib>Cheon, Dong-Joo</creatorcontrib><creatorcontrib>Gozo, Maricel C.</creatorcontrib><creatorcontrib>Beach, Jessica A.</creatorcontrib><creatorcontrib>Recouvreux, Maria Sol</creatorcontrib><creatorcontrib>Walts, Ann E.</creatorcontrib><creatorcontrib>Karlan, Beth Y.</creatorcontrib><creatorcontrib>Orsulic, Sandra</creatorcontrib><title>HOXB13 controls cell state through super-enhancers</title><title>Experimental cell research</title><addtitle>Exp Cell Res</addtitle><description>Expression of the homeodomain transcription factor HOXB13 has been demonstrated in several malignancies but its role in tumorigenesis remains elusive. We observed high levels of HOXB13 in poorly differentiated pediatric tumors including a highly aggressive childhood neoplasm - malignant rhabdoid tumor. In a xenograft model of rhabdoid tumor, knockout of HOXB13 diminished tumor growth while partial knockdown of HOXB13 promoted differentiation of tumor cells into bone. These results suggest that HOXB13 enhances rhabdoid malignancy by interfering with mesenchymal stem cell differentiation. Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. Mechanistically, we demonstrated that HOXB13 binds to super-enhancer regions regulating genes involved in differentiation and tumorigenesis.
[Display omitted]
•HOXB13 is aberrantly overexpressed in poorly differentiated sarcomas.•Knockdown of HOXB13 in a rhabdoid tumor xenograft leads to osteogenic differentiation.•Overexpression of HOXB13 inhibits differentiation of mesenchymal progenitor cells.•HOXB13 is a master transcription factor that regulates genes involved in cell state.</description><subject>Adipogenesis</subject><subject>Bone and Bones - metabolism</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - physiology</subject><subject>Differentiation</subject><subject>Gene Expression Regulation - genetics</subject><subject>Genes, Homeobox - genetics</subject><subject>Homeobox</subject><subject>Homeodomain Proteins - metabolism</subject><subject>HOXB13</subject><subject>Humans</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - cytology</subject><subject>Myogenesis</subject><subject>Osteogenesis</subject><subject>Osteogenesis - physiology</subject><subject>Rhabdoid tumor</subject><subject>Sarcoma</subject><subject>Super-enhancer</subject><subject>Transcription Factors - metabolism</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9Lw0AQxRdRbK1-AkFy9JI6-yebzcGDFrVCoRcFb8t2M7EpaVJ3N2K_vYmpHj0NPN6bN_Mj5JLClAKVN5vpHr-smzJgnUIZ8OyIjClkEDPB2DEZA1ARC8XSETnzfgMASlF5Skac8VQypcaEzZdv95RHtqmDayofWayqyAcTMApr17Tv68i3O3Qx1mtTW3T-nJwUpvJ4cZgT8vr48DKbx4vl0_PsbhFbnmQhLgRKbmjKc5lRTIRR1kolZcF5YoTspFQkiZVoV5ZlwpoCZAGpUalJpMiBT8j1sHfnmo8WfdDb0vfnmRqb1mvGs0xxlrLeygerdY33Dgu9c-XWuL2moHtYeqN_YOkelh5gdamrQ0G72mL-l_ml0xluBwN2b36W6LS3JXYQ8tKhDTpvyn8LvgEOqHog</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Aspuria, Paul-Joseph</creator><creator>Cheon, Dong-Joo</creator><creator>Gozo, Maricel C.</creator><creator>Beach, Jessica A.</creator><creator>Recouvreux, Maria Sol</creator><creator>Walts, Ann E.</creator><creator>Karlan, Beth Y.</creator><creator>Orsulic, Sandra</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope></search><sort><creationdate>20200801</creationdate><title>HOXB13 controls cell state through super-enhancers</title><author>Aspuria, Paul-Joseph ; Cheon, Dong-Joo ; Gozo, Maricel C. ; Beach, Jessica A. ; Recouvreux, Maria Sol ; Walts, Ann E. ; Karlan, Beth Y. ; Orsulic, Sandra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-f4e63a173d691e54a8cc6866f335a461e57455c6ecbc294caf06f07a87a564d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adipogenesis</topic><topic>Bone and Bones - metabolism</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - physiology</topic><topic>Differentiation</topic><topic>Gene Expression Regulation - genetics</topic><topic>Genes, Homeobox - genetics</topic><topic>Homeobox</topic><topic>Homeodomain Proteins - metabolism</topic><topic>HOXB13</topic><topic>Humans</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Myogenesis</topic><topic>Osteogenesis</topic><topic>Osteogenesis - physiology</topic><topic>Rhabdoid tumor</topic><topic>Sarcoma</topic><topic>Super-enhancer</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aspuria, Paul-Joseph</creatorcontrib><creatorcontrib>Cheon, Dong-Joo</creatorcontrib><creatorcontrib>Gozo, Maricel C.</creatorcontrib><creatorcontrib>Beach, Jessica A.</creatorcontrib><creatorcontrib>Recouvreux, Maria Sol</creatorcontrib><creatorcontrib>Walts, Ann E.</creatorcontrib><creatorcontrib>Karlan, Beth Y.</creatorcontrib><creatorcontrib>Orsulic, Sandra</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><jtitle>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aspuria, Paul-Joseph</au><au>Cheon, Dong-Joo</au><au>Gozo, Maricel C.</au><au>Beach, Jessica A.</au><au>Recouvreux, Maria Sol</au><au>Walts, Ann E.</au><au>Karlan, Beth Y.</au><au>Orsulic, Sandra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HOXB13 controls cell state through super-enhancers</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>393</volume><issue>1</issue><spage>112039</spage><epage>112039</epage><pages>112039-112039</pages><artnum>112039</artnum><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>Expression of the homeodomain transcription factor HOXB13 has been demonstrated in several malignancies but its role in tumorigenesis remains elusive. We observed high levels of HOXB13 in poorly differentiated pediatric tumors including a highly aggressive childhood neoplasm - malignant rhabdoid tumor. In a xenograft model of rhabdoid tumor, knockout of HOXB13 diminished tumor growth while partial knockdown of HOXB13 promoted differentiation of tumor cells into bone. These results suggest that HOXB13 enhances rhabdoid malignancy by interfering with mesenchymal stem cell differentiation. Consistent with this hypothesis, overexpression of HOXB13 in mesenchymal progenitor cells inhibited adipogenic, myogenic, and osteogenic differentiation. Mechanistically, we demonstrated that HOXB13 binds to super-enhancer regions regulating genes involved in differentiation and tumorigenesis.
[Display omitted]
•HOXB13 is aberrantly overexpressed in poorly differentiated sarcomas.•Knockdown of HOXB13 in a rhabdoid tumor xenograft leads to osteogenic differentiation.•Overexpression of HOXB13 inhibits differentiation of mesenchymal progenitor cells.•HOXB13 is a master transcription factor that regulates genes involved in cell state.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32376288</pmid><doi>10.1016/j.yexcr.2020.112039</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adipogenesis Bone and Bones - metabolism Cell Differentiation - genetics Cell Differentiation - physiology Differentiation Gene Expression Regulation - genetics Genes, Homeobox - genetics Homeobox Homeodomain Proteins - metabolism HOXB13 Humans Mesenchymal stem cells Mesenchymal Stem Cells - cytology Myogenesis Osteogenesis Osteogenesis - physiology Rhabdoid tumor Sarcoma Super-enhancer Transcription Factors - metabolism |
| title | HOXB13 controls cell state through super-enhancers |
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