YAP and β-catenin cooperate to drive oncogenesis in basal breast cancer


  • H.M. Quinn
  • R. Vogel
  • O. Popp
  • P. Mertins
  • L. Lan
  • C. Messerschmidt
  • A. Landshammer
  • K. Lisek
  • S. Château-Joubert
  • E. Marangoni
  • E. Koren
  • Y. Fuchs
  • W. Birchmeier


  • Cancer Research


  • Cancer Res 81 (8): 2116-2127


  • Targeting cancer stem cells (CSC) can serve as an effective approach toward limiting resistance to therapies. While basal-like (triple-negative) breast cancers encompass cells with CSC features, rational therapies remain poorly established. We show here that the receptor tyrosine kinase Met promotes YAP activity in basal-like breast cancer and find enhanced YAP activity within the CSC population. Interfering with YAP activity delayed basal-like cancer formation, prevented luminal to basal trans-differentiation, and reduced CSC. YAP knockout mammary glands revealed a decrease in β-catenin target genes, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, nuclear YAP interacted with β-catenin and TEAD4 at gene regulatory elements. Proteomic patient data revealed an upregulation of the YAP signature in basal-like breast cancers. Our findings demonstrate that in basal-like breast cancers, β-catenin activity is dependent on YAP signalling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal-like breast cancers.