c-Myb enhances breast cancer invasion and metastasis through the Wnt/β-catenin/Axin2 pathway

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Abstract

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/β-catenin signaling. c-Myb interacted with the intracellular Wnt effector β-catenin and coactivated the Wnt/β-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 c-Myb, a target of the proinflammatory cytokine IL1β that was found to be required for IL1β-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/β-catenin/Axin2 signaling.

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Li, Y., Jin, K., Van Pelt, G. W., Van Dam, H., Yu, X., Mesker, W. E., … Zhang, L. (2016). c-Myb enhances breast cancer invasion and metastasis through the Wnt/β-catenin/Axin2 pathway. Cancer Research, 76(11), 3364–3375. https://doi.org/10.1158/0008-5472.CAN-15-2302

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