Journal article
Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model
D Bakopoulos, S Golenkina, C Dark, EL Christie, BJ Sánchez-Sánchez, BM Stramer, LY Cheng
EMBO Reports | SPRINGERNATURE | Published : 2023
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 c..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We are grateful to Kieran Harvey, Helena Richardson, Gary Hime, Anne Holz, Travis Johnson, Christen Mirth, Maurice Ringuette and Ana Traven for generous sharing of fly stocks, yeast stock and antibodies. We would like to thank Bloomington Drosophila Stock Center, Vienna Drosophila Resource Center and Developmental Studies Hybridoma Bank for fly stocks and antibodies. We would like to also thank OZDros for Drosophila quarantine, Peter MacCallum Cancer Institute CAHM for microscopy assistance. We are grateful to Kellie Veen and Khanh Phuong Nguyen for assistance with graphics production. LYC's laboratory is supported by funding from the NHMRC Ideas Grant (APP1182847), and the Peter MacCallum Cancer Foundation (APP2218).