c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway

Cancer Res. 2016 Jun 1;76(11):3364-75. doi: 10.1158/0008-5472.CAN-15-2302. Epub 2016 Apr 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Axin Protein / genetics
  • Axin Protein / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-myb / genetics
  • Proto-Oncogene Proteins c-myb / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*
  • Xenograft Model Antitumor Assays
  • Zebrafish / genetics
  • Zebrafish / growth & development
  • Zebrafish / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • AXIN2 protein, human
  • Axin Protein
  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-myb
  • RNA, Messenger
  • Wnt1 Protein
  • beta Catenin