The molecular underpinnings of aggressive breast cancers remain mainly obscure. Here we demonstrate that activation of the transcription factor c-Myb is required for the prometastatic character of basal breast cancers. An analysis of breast cancer patients led us to identify c-Myb as an activator of Wnt/b-catenin signaling. c-Myb interacted with the intracellular Wnt effector b-catenin and coactivated the Wnt/b-catenin target genes Cyclin D1 and Axin2. Moreover, c-Myb controlled metastasis in an Axin2-dependent manner. Expression microarray analyses revealed a positive association between Axin2 and cMyb, a target of the proinflammatory cytokine IL1b that was found to be required for IL1b-induced breast cancer cell invasion. Overall, our results identified c-Myb as a promoter of breast cancer invasion and metastasis through its ability to activate Wnt/b-catenin/Axin2 signaling.

Background: Wnts activate transcriptional responses via stabilization and nuclear translocation of ␤-catenin. Results: FAF1 associates with SCF-␤-TrCP E3 ligase complex and promotes cytosolic ␤-catenin polyubiquitination and degradation. Conclusion: FAF1 is a scaffold protein that promotes ␤-TrCP-mediated ␤-catenin degradation. Significance: FAF1 may have tumor suppressive activity by antagonizing Wnt/␤-catenin signaling.