Lodge, W., Zavortink, M., Golenkina, S., Froldi, F., Dark, C., Cheung, S., Parker, B.L., Blazev, R., Bakopoulos, D., Christie, E.L., Wimmer, V.C., Duckworth, B.C., Richardson, H.E., Cheng, L.Y. (2021). Tumor-derived MMPs regulate cachexia in a Drosophila cancer model.  Dev. Cell 56(18): 2664--2680.e6.

FBrf0251375

Research paper

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.