Research ArticleCancer

Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple

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Science Signaling  27 Feb 2018:
Vol. 11, Issue 519, eaao4220
DOI: 10.1126/scisignal.aao4220

Growth factor and Wnt pathways cross-talk on Daple

Many proteins that maintain tissue homeostasis are conversely implicated in tumor progression. What triggers this switch? The guanine nucleotide exchange factor Daple, which coordinates Wnt and G protein signals, acts as a tumor suppressor in the normal epithelium and early-stage tumors but facilitates metastatic progression in advanced tumors. Aznar et al. found that growth factor receptor activation, frequently observed in many cancers, phosphorylated a critical protein interaction motif in Daple that enhanced its binding to G proteins rather than to a Wnt receptor inhibitor, thereby stimulating ligand-independent Wnt signaling. Supported by protein signatures in colorectal tumors from patients, these findings suggest that concurrent activation of Wnt and growth factor receptor pathways fuels a Daple-mediated switch to cancer progression.

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