• intestinal cancer

The Drosophila posterior midgut is closely analogous to the mammalian small intestine; the midgut epithelium is maintained by frequent division of self-renewing intestinal stem cells (ISCs). This system has been extensively characterized in the context of general models of epithelial homeostasis. Developmental signals and signaling pathways, including signaling within the local microenvironment, have been characterized.

Development of differentiated absorptive and secretory gut cell types requires Notch signaling; loss of Notch (N) function in the posterior midgut results in stem cell tumor formation. See the human disease model report 'cancer, intestinal stem cell, NOTCH-related' (FBhh0001354).

Drosophila adult stem cells have been found to be resistant to radiation- or chemical-induced apoptosis, thus providing a means to investigate mechanisms of resistance of stem cell tumors to various anticancer therapies.

This system has been used to characterize regulation of mitochondrial pyruvate metabolism in stem cell maintenance and differentiation and the role of Dmel\Mpc1 (ortholog of human MPC1) in that process.

The intestinal stem cell model has also been used to study colorectal cancer, by expressing implicated genes or gene variants in ISCs. See human disease model reports listed in "Related Diseases" section, below, for additional models based on this system.

[updated Mar 2021 by FlyBase; FBrf0222196]