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c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/beta-Catenin/Axin2 Pathway
Zhejiang Univ, Inst Life Sci, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China.;Zhejiang Univ, Innovat Ctr Cell Signaling Network, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China.;Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, Dept Mol Cell Biol, Leiden, Netherlands..
Zhejiang Univ, Inst Life Sci, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China.;Zhejiang Univ, Innovat Ctr Cell Signaling Network, 866 Yuhangtang Rd, Hangzhou 310058, Zhejiang, Peoples R China..
Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Leiden Univ, Med Ctr, Canc Genom Ctr Netherlands, Dept Mol Cell Biol, Leiden, Netherlands..
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2016 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 76, no 11, 3364-3375 p.Article in journal (Refereed) PublishedText
Abstract [en]

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/beta-catenin signaling. c-Myb interacted with the intracellular Wnt effector beta-catenin and coactivated the Wnt/beta-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 IL1 beta that was found to be required for IL1 beta-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/beta-catenin/Axin2 signaling. (C) 2016 AACR.

Place, publisher, year, edition, pages
2016. Vol. 76, no 11, 3364-3375 p.
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-299730DOI: 10.1158/0008-5472.CAN-15-2302ISI: 000378060900026PubMedID: 27197202OAI: oai:DiVA.org:uu-299730DiVA: diva2:949990
Funder
Swedish Cancer Society, 09 0773
Available from: 2016-07-26 Created: 2016-07-26 Last updated: 2016-07-26Bibliographically approved

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