Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model
- Author(s)
- Bakopoulos, D; Golenkina, S; Dark, C; Christie, EL; Sánchez-Sánchez, BJ; Stramer, BM; Cheng, LY;
- Details
- Publication Year 2023-11-28,Volume 24,Issue #12,Page e57695
- Journal Title
- EMBO Reports
- Publication Type
- Research article
- 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.
- Publisher
- Springer Nature
- Keywords
- Drosophila; Ecm; Tgf-β; cachexia; insulin
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.15252/embr.202357695
- Open Access at Publisher's Site
https://doi.org/10.15252/embr.202357695- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-12-11 11:25:05
Last Modified: 2023-12-11 11:28:19