RRC ID 67945
Author 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.
Title Tumor-derived MMPs regulate cachexia in a Drosophila cancer model.
Journal Dev 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.
Volume 56(18)
Pages 2664-2680.e6
Published 2021-9-27
DOI 10.1016/j.devcel.2021.08.008
PII S1534-5807(21)00638-9
PMID 34473940
MeSH Adipose Tissue / metabolism* Animals Basement Membrane / metabolism Drosophila / metabolism Extracellular Matrix / metabolism Matrix Metalloproteinases / metabolism* Muscle, Skeletal / metabolism* Muscular Atrophy / metabolism Neoplasms / metabolism*
IF 10.092
Drosophila 4859R-1 7549R-1 7103R-2 5988R-1 DGRC#115429 DGRC#110692