Suppression of kinesin expression disrupts adenomatous polyposis coli (APC) localization and affects β-catenin turnover in young adult mouse colon (YAMC) epithelial cells

Mutational inactivation of the adenomatous polyposis coli (APC) protein initiates most hereditary and sporadic colon cancers. The tumor-suppressive effect of APC is mediated by promoting degradation of the oncogenic transcriptional activator beta-catenin, and loss of APC function often results in nuclear accumulation of beta-catenin in cancer cells. A-PC is a nuclear-cytoplasmic shuttling protein and moves along microtubules in the cytoplasm. However, the molecular motor proteins responsible for A-PC translocation and the implications of AIPC trafficking on beta-catenin turnover are unknown. Here we show that A-PC protein is associated with microtubules and is colocalized with kinesin heavy chain (KHC) and beta-catenin to clusters of puncta at the tip regions of cellular extensions in a conditionally immortalized mouse colon epithelial cell line, young adult mouse colon (YAMC, APC+/+). Inhibition of KHC expression using an antisense oligonucleotide disrupts peripheral translocation of APC and induces nucleocytoplasmic accumulation of beta-catenin. These data indicate that KHC-mediated A-PC translocation is tightly coordinated with beta-catenin turnover in the cell. (C) 2002 Elsevier Science (USA).