Mutated APC and Asef are involved in the migration of colorectal tumour cells

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Abstract
The tumour suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumours1,2. APC binds to β-catenin, a key component of the Wnt signalling pathway, and induces its degradation1,2,3,4,5. APC interacts with microtubules and accumulates at their plus ends in membrane protrusions6,7,8,9, and associates with the plasma membrane in an actin-dependent manner10. In addition, APC interacts with the Rac-specific guanine nucleotide exchange factor Asef and stimulates its activity, thereby regulating the actin cytoskeletal network and cell morphology11. Here we show that overexpression of Asef decreases E-cadherin-mediated cell–cell adhesion and promotes the migration of epithelial Madin–Darby canine kidney cells. Both of these activities are stimulated by truncated APC proteins expressed in colorectal tumour cells. Experiments based on RNA interference and dominant-negative mutants show that both Asef and mutated APC are required for the migration of colorectal tumour cells expressing truncated APC. These results suggest that the APC–Asef complex functions in cell migration as well as in E-cadherin-mediated cell–cell adhesion, and that truncated APC present in colorectal tumour cells contributes to their aberrant migratory properties.