title: c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway.
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. Cancer Res; 76(11); 3364-75. ©2016 AACR.
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China. Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Jin
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Gabi W
authors.initials: GW
authors.lastname: van Pelt
authors.affiliation: Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Leiden, the Netherlands. Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: van Dam
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Wilma E
authors.initials: WE
authors.lastname: Mesker
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China. Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Leiden, the Netherlands. Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Ten Dijke
authors.affiliation: Institutes of Biology and Medical Science, Soochow University, Suzhou, P.R. China. l_zhang@zju.edu.cn zhoufangfang@suda.edu.cn.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, China. l_zhang@zju.edu.cn zhoufangfang@suda.edu.cn.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D014408:Biomarkers, Tumor; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D051155:Wnt1 Protein; D051176:beta Catenin