Reference - Detail
| 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 |
| Resource | |
| Drosophila | 4859R-1 7549R-1 7103R-2 5988R-1 DGRC#115429 DGRC#110692 |