(A) Strength of Wnt signaling is measured by TOPflash assay, as described (2) upon treatment with inhibitors A939572, TMP-153 or Oleate for 16 hours followed by the addition of Wnt3a for 24 hours. (n=4 for each represented treatments). Y axis, Luc/Rluc. ratio of luciferase (Luc) units over Renilla luciferase (RLuc) in inhibitor-treated groups is normalized to vehicle. P value for pairwise comparisons a, b, c is represented on the graph. P value <0.0001 represented as “****” and P value that are <0.05 is represented as “*”.
(B) Model: Runx1 modulates levels of Scd1 and Soat1 and its products oleate and cholesterol esters to regulate proliferation in part through membrane organization (or fluidity). Scd1 activity and oleate concentration in the plasma membrane phospholipids in turn alters Wnt activity resulting in higher responsiveness to signals and enhanced cell proliferation.