Figure 4

Mutations in APC gene impair actin cytoskeletal integrity, cell-cell adhesion and cell migration properties of colon cancer cells. Panel A shows the organization of cell-cell adhesion and cytoskeletal proteins in normal colonic epithelial cells. The APC gene product is shown to bind through its armadillo repeat domain to ASEF. Endogenous APC co-localizes with ASEF in colonic epithelial cells. APC regulates guanine nucleotide exchange factor (GEF) activity of ASEF and maintains actin cytoskeletal network, cell-cell adhesion and cell migration. Panel B shows how mutations in the APC gene product may impair actin cytoskeletal network, cell-cell adhesion and cell migration properties of colon cancer cells. Mutations in APC gene product disrupt binding with actin and β-catenin; thus it affects actin cytoskeletal network and cell-cell adhesion, respectively. ASEF binds with most APC mutant proteins containing armadillo repeat sites, stimulates its own GEF activity, and promotes cell migration.