Most colorectal cancers carry inactivating mutations in adenomatous polyposis coli (APC), a negative regulator of Wnt signalling. Moreover, in mice, Apc inactivation is sufficient to drive intestinal hyperplasia. Now, Julia Cordero, Owen Sansom and colleagues use the adult Drosophila midgut to identify the signalling pathways that mediate intestinal hyperplasia following Apc loss (see ). The researchers show that the Wnt target Myc is required for Drosophila intestinal stem cell (ISC) hyperproliferation following Apc1 loss. Egfr and Jak/Stat signalling are both activated in a Myc-dependent manner following Apc1 loss, they report, and are required to drive ISC hyperproliferation. Notably, Apc1 loss in ISCs results in non-cell-autonomous upregulation of the interleukin-like ligands Upd2/3 in enterocytes and subsequent activation of Jak/Stat signalling in ISCs. These and other findings indicate that non-cell-autonomous crosstalk between the Wnt/Myc, Egfr and Jak/Stat signalling pathways regulates intestinal hyperproliferation in the Drosophila midgut following Apc1 loss and suggest that these pathways may also be activated in human colorectal cancers.
