Tumor-derived MMPs regulate cachexia in a Drosophila cancer model.
Version 2 2022-03-25, 03:50Version 2 2022-03-25, 03:50
Version 1 2022-03-25, 03:48Version 1 2022-03-25, 03:48
journal contribution
posted on 2022-03-25, 03:50authored byWilliam Lodge, Michael Zavortink, Sofia Golenkina, Francesca Froldi, Callum Dark, Shane Cheung, Benjamin L Parker, Ronnie Blazev, Daniel Bakopoulos, Elizabeth L Christie, Verena C Wimmer, Brigette C Duckworth, Helena RichardsonHelena Richardson, Louise Y Cheng
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.
Funding
L.Y.C. is funded by an ARC Future fellowship FT80100255, L.Y.C.'s laboratory is supported by funding from the NHMRC, ARC and the Peter MacCallum Cancer Foundation.
History
Publication Date
2021-09-27
Journal
Developmental Cell
Volume
56
Issue
18
Pagination
24p. (graphical abstract, p. 2664-2680, report e1-e6)