Convergent Insulin and TGF-ß signalling drives cancer cachexia by promoting aberrant fatbody ECM accumulation in a Drosophila tumour model
Convergent Insulin and TGF-ß signalling drives cancer cachexia by promoting aberrant fatbody ECM accumulation in a Drosophila tumour model
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果蝇肿瘤模型中，胰岛素和 TGF-β 信号趋同通过促进异常脂肪体 ECM 积累来驱动癌症恶病质
DOI：
10.1101/2023.06.10.544444
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bakopoulos D
中科院分区：
文献类型：
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作者：
Bakopoulos D
在这项研究中，我们发现，在野生型动物的脂肪组织中，胰岛素和TGF-β信号转导通过BMP拮抗剂短原肠胚形成（sog）会聚，以调节ECM重塑。在荷瘤动物中，Sog还调节TGF-β信号传导以调节ECM在脂肪体中的积累。TGF-β信号传导导致ECM保留在脂肪体中，随后消耗脂肪体来源的ECM蛋白的肌肉。胰岛素信号传导的激活、TGF-β信号传导的抑制或通过脂肪体中的Rab、Rab 10或胶原蛋白IV调节ECM水平，能够在存在肿瘤的情况下挽救组织消耗。总之，我们的研究强调了脂肪ECM重塑在癌症恶病质背景下的重要性。
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.