Is. Nathke et al., THE ADENOMATOUS POLYPOSIS-COLI TUMOR-SUPPRESSOR PROTEIN LOCALIZES TO PLASMA-MEMBRANE SITES INVOLVED IN ACTIVE CELL-MIGRATION, The Journal of cell biology, 134(1), 1996, pp. 165-179
Mutations in the adenomatous polyposis coli (APC) gene are linked to p
olyp formation in familial and sporadic colon cancer, but the function
s of the protein are not known. We show that APC protein localizes mai
nly to clusters of puncta near the ends of microtubules that extend in
to actively migrating regions of epithelial cell membranes, This subce
llular distribution of APC protein requires microtubules, but not acti
n filaments. APC protein-containing membranes are actively involved in
cell migration in response to wounding epithelial monolayers, additio
n of the motorgen hepatocyte growth factor, and during the formation o
f cell-cell contacts, In the intestine, APC protein levels increase at
the crypt/villus boundary, where cell migration is crucial for entero
cyte exit from the crypt and where cells accumulate during polyp forma
tion that is linked to mutations in the microtubule-binding domain of
APC protein. Together, these data indicate that APC protein has a role
in directed cell migration.