Cell Reports
Volume 13, Issue 3, 20 October 2015, Pages 495-503
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Unsaturated Fatty Acids Stimulate Tumor Growth through Stabilization of β-Catenin

https://doi.org/10.1016/j.celrep.2015.09.010Get rights and content
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Highlights

  • Unsaturated fatty acids (uFAs) inhibit β-catenin degradation by inactivating FAF1

  • β-catenin degradation can be independently inhibited by Wnt signaling and uFAs

  • uFAs promote growth of kidney cancers by stabilization of β-catenin

Summary

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. Here, we 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.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).