Tumor-derived MMPs regulate cachexia in a Drosophila cancer model
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
WEHI Research Division(s)
Advanced Technology And Biology
PubMed ID
34473940
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
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