This report describes a tumor model using an activated form of Dmel\yki expressed in the developing eye and the use of this model to investigate the phenomenon of cachexia. Dmel\yki is orthologous to human YAP1 and is a core component of the Hippo Signaling Pathway (FBgg0000913); see the human disease model report 'cancer, multiple, Hippo signaling pathway' (FBhh0000764).
Overexpression of wild-type yki in the developing eye causes a mild rough eye phenotype; overexpression of the constitutively active form results in a dramatic protrusion of the eyes caused by excessive cell proliferation. The eye was used, in part, to minimize direct effects on feeding behavior. In the fly eye cancer model, a mild wasting phenotype in the ovary and reduced triglyceride levels in the fat tissues is observed up to 10 days, and a severe wasting phenotype develops after 15–20 days. The thoracic muscle of 15-day-old affected adult flies shows an abnormal mitochondrial structure with irregular packing of mitochondria between the muscle fibers, which indicates the muscle wasting phenotype. The flies also show reduced food intake after five days, indicating that cancer anorexia precedes cachexia-like organ wasting in this system. The role of Dmel\Ilp8 (putative ortholog of human INSL3) in the cancer-induced anorexia behavior has been investigated in this system.
For an additional models of cachexia in flies, see the human disease model report 'cachexia, IGFBP-related' (FBhh0000535) and 'cachexia, yki-induced ISC tumor model' (FBhh0001115). The Warburg effect (preferential use of aerobic glycolysis by cancer cells) may be one of the contributing factors in the development of cachexia. See human disease model reports 'cancer, aerobic glycolysis (Warburg effect), larval growth ' (FBhh0000502) and 'cancer, epithelial, glycolytic tumor model' (FBhh0000959).
[updated Feb. 2021 by FlyBase; FBrf0222196]
Cachexia is characterized by a dramatic loss of skeletal muscle mass and adipose tissue, resulting in substantial weight loss. It is also known as "wasting syndrome", causing disproportionate muscle wasting, weakness, fatigue, and loss of appetite in affected individuals. Cachexia occurs in many cancers, usually at the advanced stages of disease. [ http://www.news-medical.net/health/Cachexia-Wasting-Syndrome-.aspx ] [ https://www.cancer.gov/about-cancer/treatment/research/cachexia ]
Moderate-scoring ortholog of human YAP1; lower-scoring ortholog of WWTR1 (1 Drosophila to 2 human). Dmel\yki shares 31% identity and 45% similarity with YAP1; it shares 25% identity and 34% similarity with WWTR1.