Unsaturated fatty acids stimulate tumor growth through stabilization of β-catenin

Unsaturated fatty acids stimulate tumor growth through stabilization of β-catenin
 

Some cancer cells exhibit elevated levels of free fatty acids (FAs) as well as high levels of β-catenin, a transcriptional co-activator that promotes their growth.

In an article published in Cell Reports, the authors link these two phenomena by showing that unsaturated FAs inhibit degradation of β-catenin. Unsaturated FAs bind to the UAS domain of Fas-associated factor 1 (FAF1), a protein known to bind β-catenin, accelerating its degradation.

FA binding disrupts the FAF1/β-catenin complex, preventing proteasomal degradation of ubiquitinated β-catenin. This mechanism for stabilization of β-catenin differs from that of Wnt signaling, which blocks ubiquitination of β-catenin.

In clear cell renal cell carcinoma (ccRCC) cells, unsaturated FAs stimulated cell proliferation through stabilization of β-catenin. In tissues from biopsies of human ccRCC, elevated levels of unsaturated FAs correlated with increased levels of β-catenin.

Thus, targeting FAF1 may be an effective approach to treat cancers that exhibit elevated FAs and β-catenin.

http://www.cell.com/cell-reports/abstract/S2211-1247(15)01021-9

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