Unsaturated Fatty Acids Stimulate Tumor Growth through Stabilization of β-Catenin

Cell Rep. 2015 Oct 20;13(3):495-503. doi: 10.1016/j.celrep.2015.09.010. Epub 2015 Oct 8.


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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis Regulatory Proteins
  • CHO Cells
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Fatty Acids, Unsaturated / metabolism*
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein Stability
  • Proteolysis
  • Ubiquitination
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • FAF1 protein, human
  • Fatty Acids, Unsaturated
  • beta Catenin
  • Proteasome Endopeptidase Complex