Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model

Daniel Bakopoulos; Sofya Golenkina; Callum Dark; Elizabeth L. Christie; Besaiz J. Sánchez-Sánchez; Brian M. Stramer; Louise Y. Cheng

doi:10.15252/embr.202357695

Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model

Daniel Bakopoulos, Sofya Golenkina, Callum Dark, Elizabeth L. Christie, Besaiz J. Sánchez-Sánchez, Brian M. Stramer, Louise Y. Cheng^*

^*Corresponding author for this work

Randall Centre of Cell & Molecular Biophysics

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Article number	e57695
Journal	EMBO reports
Volume	24
Issue number	12
DOIs	https://doi.org/10.15252/embr.202357695
Publication status	Published - 6 Dec 2023

Keywords

cachexia
Drosophila
ECM
insulin
TGF-β

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.15252/embr.202357695

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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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AU - Christie, Elizabeth L.

AU - Sánchez-Sánchez, Besaiz J.

AU - Stramer, Brian M.

AU - Cheng, Louise Y.

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AB - 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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Convergent insulin and TGF-β signalling drives cancer cachexia by promoting aberrant fat body ECM accumulation in a Drosophila tumour model

Abstract

Keywords

UN SDGs

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