Convergent insulin and TGF‐β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model
In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF‐β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF‐β signalling to regulate ECM accumulation in the fat body. TGF‐β...
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| Veröffentlicht in: | EMBO reports 2023-12, Vol.24 (12), p.e57695-n/a |
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| creator | Bakopoulos, Daniel Golenkina, Sofya Dark, Callum Christie, Elizabeth L Sánchez‐Sánchez, Besaiz J Stramer, Brian M Cheng, Louise Y |
| description | In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF‐β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF‐β signalling to regulate ECM accumulation in the fat body. TGF‐β signalling causes ECM retention in the fat body and subsequently depletes muscles of fat body‐derived ECM proteins. Activation of insulin signalling, inhibition of TGF‐β signalling, or modulation of ECM levels via SPARC, Rab10 or Collagen IV in the fat body, is able to rescue tissue wasting in the presence of tumour. Together, our study highlights the importance of adipose ECM remodelling in the context of cancer cachexia.
Synopsis
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity.
Eye tumour models employing RasV12 together with Scrib RNAi or Dlg RNAi were used to study how inter‐organ communication affects fat body and muscle integrity in cancer cachexia.
TGF‐β and insulin signalling converge in the fat body to control ECM secretion via Sog.
Modulating ECM secretion from the fat body rescues muscle integrity in the presence of tumour.
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity. |
| doi_str_mv | 10.15252/embr.202357695 |
| format | Article |
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Synopsis
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity.
Eye tumour models employing RasV12 together with Scrib RNAi or Dlg RNAi were used to study how inter‐organ communication affects fat body and muscle integrity in cancer cachexia.
TGF‐β and insulin signalling converge in the fat body to control ECM secretion via Sog.
Modulating ECM secretion from the fat body rescues muscle integrity in the presence of tumour.
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity.</description><identifier>ISSN: 1469-221X</identifier><identifier>EISSN: 1469-3178</identifier><identifier>DOI: 10.15252/embr.202357695</identifier><identifier>PMID: 38014610</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Accumulation ; Adipose tissue ; Adipose Tissue - metabolism ; Animals ; Antagonists ; Body fat ; Cachexia ; Cachexia - etiology ; Cachexia - metabolism ; Cancer ; Cell signaling ; Collagen ; Collagen (type IV) ; Convergence ; Drosophila ; ECM ; Fat body ; Fat Body - metabolism ; Gastrulation ; Insulin ; Integrity ; Muscle strength ; Muscles ; Neoplasms - complications ; Osteonectin ; RNA-mediated interference ; Secretion ; TGF‐β ; Transforming Growth Factor beta ; Transforming growth factor-b ; Tumors</subject><ispartof>EMBO reports, 2023-12, Vol.24 (12), p.e57695-n/a</ispartof><rights>2023 The Authors. Published under the terms of the CC BY 4.0 license</rights><rights>2023 The Authors. Published under the terms of the CC BY 4.0 license.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4175-8e54da7f4b8df8a1702805c75e7829c8d057218578028d254488426f7e7c50b53</citedby><cites>FETCH-LOGICAL-c4175-8e54da7f4b8df8a1702805c75e7829c8d057218578028d254488426f7e7c50b53</cites><orcidid>0000-0001-7034-3269 ; 0000-0001-9712-4082 ; 0000-0002-9959-7024 ; 0000-0001-7934-5236 ; 0000-0003-1935-3503</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.15252%2Fembr.202357695$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.15252%2Fembr.202357695$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,1418,1434,27926,27927,45576,45577,46411,46835</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38014610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bakopoulos, Daniel</creatorcontrib><creatorcontrib>Golenkina, Sofya</creatorcontrib><creatorcontrib>Dark, Callum</creatorcontrib><creatorcontrib>Christie, Elizabeth L</creatorcontrib><creatorcontrib>Sánchez‐Sánchez, Besaiz J</creatorcontrib><creatorcontrib>Stramer, Brian M</creatorcontrib><creatorcontrib>Cheng, Louise Y</creatorcontrib><title>Convergent insulin and TGF‐β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model</title><title>EMBO reports</title><addtitle>EMBO Rep</addtitle><description>In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF‐β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF‐β signalling to regulate ECM accumulation in the fat body. TGF‐β signalling causes ECM retention in the fat body and subsequently depletes muscles of fat body‐derived ECM proteins. Activation of insulin signalling, inhibition of TGF‐β signalling, or modulation of ECM levels via SPARC, Rab10 or Collagen IV in the fat body, is able to rescue tissue wasting in the presence of tumour. Together, our study highlights the importance of adipose ECM remodelling in the context of cancer cachexia.
Synopsis
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity.
Eye tumour models employing RasV12 together with Scrib RNAi or Dlg RNAi were used to study how inter‐organ communication affects fat body and muscle integrity in cancer cachexia.
TGF‐β and insulin signalling converge in the fat body to control ECM secretion via Sog.
Modulating ECM secretion from the fat body rescues muscle integrity in the presence of tumour.
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity.</description><subject>Accumulation</subject><subject>Adipose tissue</subject><subject>Adipose Tissue - metabolism</subject><subject>Animals</subject><subject>Antagonists</subject><subject>Body fat</subject><subject>Cachexia</subject><subject>Cachexia - etiology</subject><subject>Cachexia - metabolism</subject><subject>Cancer</subject><subject>Cell signaling</subject><subject>Collagen</subject><subject>Collagen (type IV)</subject><subject>Convergence</subject><subject>Drosophila</subject><subject>ECM</subject><subject>Fat body</subject><subject>Fat Body - metabolism</subject><subject>Gastrulation</subject><subject>Insulin</subject><subject>Integrity</subject><subject>Muscle strength</subject><subject>Muscles</subject><subject>Neoplasms - complications</subject><subject>Osteonectin</subject><subject>RNA-mediated interference</subject><subject>Secretion</subject><subject>TGF‐β</subject><subject>Transforming Growth Factor beta</subject><subject>Transforming growth factor-b</subject><subject>Tumors</subject><issn>1469-221X</issn><issn>1469-3178</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkU1uFDEQhS0EIj-wZocssWEzie22x252ZJgEpERIKEjsWm67euLIbQ92d2B2OQHiLByEQ3AS3JkhSGxYlVX11atyPYSeUXJEBRPsGPo2HTHCKiHntXiA9imf17OKSvVw92aMftpDBzlfE0JELdVjtFcpUmqU7KNvixhuIK0gDNiFPHoXsA4WX56d_rr9_vMHzm4VtC_pFbbJ3UDGRgcDqQRzBV-dxu0Gr1Ps4zAxuoWUdBHr9IDbaDd4ubjA2pixH70eXAx4moDfpJjj-sp5jYexj2PCfbTgn6BHnfYZnu7iIfp4urxcvJ2dvz97t3h9PjOcSjFTILjVsuOtsp3SVBKmiDBSgFSsNsoSIRlVQqpSsExwrhRn806CNIK0ojpEL7e6ZfPPI-Sh6V024L0OEMfcMFVzyXglJ_TFP-h1Wbfc5I6qmZqOWajjLWXKx3KCrlkn1-u0aShp7qxqJquae6tKx_Od7tj2YO_5P94U4NUW-OI8bP6n1ywvTj78Vf8NEduimg</recordid><startdate>20231206</startdate><enddate>20231206</enddate><creator>Bakopoulos, Daniel</creator><creator>Golenkina, Sofya</creator><creator>Dark, Callum</creator><creator>Christie, Elizabeth L</creator><creator>Sánchez‐Sánchez, Besaiz J</creator><creator>Stramer, Brian M</creator><creator>Cheng, Louise Y</creator><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>WIN</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>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7034-3269</orcidid><orcidid>https://orcid.org/0000-0001-9712-4082</orcidid><orcidid>https://orcid.org/0000-0002-9959-7024</orcidid><orcidid>https://orcid.org/0000-0001-7934-5236</orcidid><orcidid>https://orcid.org/0000-0003-1935-3503</orcidid></search><sort><creationdate>20231206</creationdate><title>Convergent insulin and TGF‐β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model</title><author>Bakopoulos, Daniel ; Golenkina, Sofya ; Dark, Callum ; Christie, Elizabeth L ; Sánchez‐Sánchez, Besaiz J ; Stramer, Brian M ; Cheng, Louise Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4175-8e54da7f4b8df8a1702805c75e7829c8d057218578028d254488426f7e7c50b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Accumulation</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - metabolism</topic><topic>Animals</topic><topic>Antagonists</topic><topic>Body fat</topic><topic>Cachexia</topic><topic>Cachexia - etiology</topic><topic>Cachexia - metabolism</topic><topic>Cancer</topic><topic>Cell signaling</topic><topic>Collagen</topic><topic>Collagen (type IV)</topic><topic>Convergence</topic><topic>Drosophila</topic><topic>ECM</topic><topic>Fat body</topic><topic>Fat Body - metabolism</topic><topic>Gastrulation</topic><topic>Insulin</topic><topic>Integrity</topic><topic>Muscle strength</topic><topic>Muscles</topic><topic>Neoplasms - complications</topic><topic>Osteonectin</topic><topic>RNA-mediated interference</topic><topic>Secretion</topic><topic>TGF‐β</topic><topic>Transforming Growth Factor beta</topic><topic>Transforming growth factor-b</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bakopoulos, Daniel</creatorcontrib><creatorcontrib>Golenkina, Sofya</creatorcontrib><creatorcontrib>Dark, Callum</creatorcontrib><creatorcontrib>Christie, Elizabeth L</creatorcontrib><creatorcontrib>Sánchez‐Sánchez, Besaiz J</creatorcontrib><creatorcontrib>Stramer, Brian M</creatorcontrib><creatorcontrib>Cheng, Louise Y</creatorcontrib><collection>Wiley-Blackwell Open Access Collection</collection><collection>Wiley Free Archive</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>EMBO reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bakopoulos, Daniel</au><au>Golenkina, Sofya</au><au>Dark, Callum</au><au>Christie, Elizabeth L</au><au>Sánchez‐Sánchez, Besaiz J</au><au>Stramer, Brian M</au><au>Cheng, Louise Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Convergent insulin and TGF‐β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model</atitle><jtitle>EMBO reports</jtitle><addtitle>EMBO Rep</addtitle><date>2023-12-06</date><risdate>2023</risdate><volume>24</volume><issue>12</issue><spage>e57695</spage><epage>n/a</epage><pages>e57695-n/a</pages><issn>1469-221X</issn><eissn>1469-3178</eissn><abstract>In this study, we found that in the adipose tissue of wildtype animals, insulin and TGF‐β signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF‐β signalling to regulate ECM accumulation in the fat body. TGF‐β signalling causes ECM retention in the fat body and subsequently depletes muscles of fat body‐derived ECM proteins. Activation of insulin signalling, inhibition of TGF‐β signalling, or modulation of ECM levels via SPARC, Rab10 or Collagen IV in the fat body, is able to rescue tissue wasting in the presence of tumour. Together, our study highlights the importance of adipose ECM remodelling in the context of cancer cachexia.
Synopsis
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity.
Eye tumour models employing RasV12 together with Scrib RNAi or Dlg RNAi were used to study how inter‐organ communication affects fat body and muscle integrity in cancer cachexia.
TGF‐β and insulin signalling converge in the fat body to control ECM secretion via Sog.
Modulating ECM secretion from the fat body rescues muscle integrity in the presence of tumour.
During cancer cachexia, insulin and TGF‐β signalling converge in the fat body via Sog to hinder ECM secretion, which in turn affects muscle integrity.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>38014610</pmid><doi>10.15252/embr.202357695</doi><tpages>26</tpages><orcidid>https://orcid.org/0000-0001-7034-3269</orcidid><orcidid>https://orcid.org/0000-0001-9712-4082</orcidid><orcidid>https://orcid.org/0000-0002-9959-7024</orcidid><orcidid>https://orcid.org/0000-0001-7934-5236</orcidid><orcidid>https://orcid.org/0000-0003-1935-3503</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley-Blackwell Journals; Open Access: PubMed Central; MEDLINE; Wiley Free Archive; Springer Nature OA Free Journals; EZB Electronic Journals Library |
| subjects | Accumulation Adipose tissue Adipose Tissue - metabolism Animals Antagonists Body fat Cachexia Cachexia - etiology Cachexia - metabolism Cancer Cell signaling Collagen Collagen (type IV) Convergence Drosophila ECM Fat body Fat Body - metabolism Gastrulation Insulin Integrity Muscle strength Muscles Neoplasms - complications Osteonectin RNA-mediated interference Secretion TGF‐β Transforming Growth Factor beta Transforming growth factor-b Tumors |
| title | Convergent insulin and TGF‐β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model |
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