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-beta signalling converge via a BMP antagonist short gastrulation (sog) to regulate ECM remodelling. In tumour bearing animals, Sog also modulates TGF-beta signalling to regulate ECM accumulation in the fat body. TGF-beta 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-beta 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.

Automated summary

This study shows that insulin and TGF-beta signalling converge via a BMP antagonist sog to regulate ECM remodelling in adipose tissue. In tumour bearing animals, Sog also modulates TGF-beta signalling to regulate ECM accumulation. Activation of insulin signalling, inhibition of TGF-beta signalling, or modulation of ECM levels can rescue tissue wasting in the presence of tumor.