Tumor-derived MMPs regulate cachexia in a Drosophila cancer model
- Author(s)
- Lodge, W; Zavortink, M; Golenkina, S; Froldi, F; Dark, C; Cheung, S; Parker, BL; Blazev, R; Bakopoulos, D; Christie, EL; Wimmer, VC; Duckworth, BC; Richardson, HE; Cheng, LY;
- Journal Title
- Developmental Cell
- Abstract
- Cachexia, the wasting syndrome commonly observed in advanced cancer patients, accounts for up to one-third of cancer-related mortalities. We have established a Drosophila larval model of organ wasting whereby epithelial overgrowth in eye-antennal discs leads to wasting of the adipose tissue and muscles. The wasting is associated with fat-body remodeling and muscle detachment and is dependent on tumor-secreted matrix metalloproteinase 1 (Mmp1). Mmp1 can both modulate TGFβ signaling in the fat body and disrupt basement membrane (BM)/extracellular matrix (ECM) protein localization in both the fat body and the muscle. Inhibition of TGFβ signaling or Mmps in the fat body/muscle using a QF2-QUAS binary expression system rescues muscle wasting in the presence of tumor. Altogether, our study proposes that tumor-derived Mmps are central mediators of organ wasting in cancer cachexia.
- Publisher
- Cell Press
- Keywords
- Drosophila; Mmp; TGFβ signaling; Timp; cachexia; fat body; interorgan crosstalk; muscle
- Research Division(s)
- Advanced Technology And Biology
- PubMed ID
- 34473940
- Publisher's Version
- https://doi.org/10.1016/j.devcel.2021.08.008
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-09-17 11:23:19
Last Modified: 2021-09-17 11:50:42