Unsaturated Fatty Acids Stimulate Tumor Growth through Stabilization of ?-Catenin.

ABSTRACT: Some cancer cells exhibit elevated levels of free fatty acids (FAs) as well as high levels of ?-catenin, a transcriptional co-activator that promotes their growth. Here, we link these two phenomena by showing that unsaturated FAs inhibit degradation of ?-catenin. Unsaturated FAs bind to the UAS domain of Fas-associated factor 1 (FAF1), a protein known to bind ?-catenin, accelerating its degradation. FA binding disrupts the FAF1/?-catenin complex, preventing proteasomal degradation of ubiquitinated ?-catenin. This mechanism for stabilization of ?-catenin differs from that of Wnt signaling, which blocks ubiquitination of ?-catenin. In clear cell renal cell carcinoma (ccRCC) cells, unsaturated FAs stimulated cell proliferation through stabilization of ?-catenin. In tissues from biopsies of human ccRCC, elevated levels of unsaturated FAs correlated with increased levels of ?-catenin. Thus, targeting FAF1 may be an effective approach to treat cancers that exhibit elevated FAs and ?-catenin.

SUBMITTER: Kim H 

PROVIDER: S-EPMC4618234 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature