Mutated APC and Asef are involved in the migration of colorectal tumour cells.
The tumour suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumours. APC binds to beta-catenin, a key component of the Wnt signalling pathway, and induces its degradation. APC interacts with microtubules and accumulates at their plus ends in membrane protrusions, and associates with the plasma membrane in an actin-dependent manner. 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 morphology. 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.
Kawasaki
Yoshihiro
Y
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.
Sato
Rina
R
Akiyama
Tetsu
T
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D015179:Colorectal Neoplasms / Q000473:pathology*; D017931:DNA Primers; D004285:Dogs; D017491:Genes, APC; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D011233:Precipitin Tests; D064067:Rho Guanine Nucleotide Exchange Factors
D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors