Article ; Online: Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model.
2023 Volume 24, Issue 12, Page(s) e57695
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 ... ...
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. |
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MeSH term(s) | Animals ; Cachexia/etiology ; Cachexia/metabolism ; Drosophila ; Insulin ; Fat Body/metabolism ; Adipose Tissue/metabolism ; Transforming Growth Factor beta ; Neoplasms/complications |
Chemical Substances | Insulin ; Transforming Growth Factor beta |
Language | English |
Publishing date | 2023-11-28 |
Publishing country | England |
Document type | Journal Article |
ZDB-ID | 2020896-0 |
ISSN | 1469-3178 ; 1469-221X |
ISSN (online) | 1469-3178 |
ISSN | 1469-221X |
DOI | 10.15252/embr.202357695 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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