DNER promotes epithelial-mesenchymal transition and prevents chemosensitivity through the Wnt/β-catenin pathway in breast cancer

Cell Death Dis. 2020 Aug 18;11(8):642. doi: 10.1038/s41419-020-02903-1.


Breast cancer (BC) is the most common malignant tumour in women worldwide, and one of the most common fatal tumours in women. Delta/Notch-like epidermal growth factor (EGF)-related receptor (DNER) is a transmembrane protein involved in the development of tumours. The role and potential mechanism of DNER in epithelial-mesenchymal transition (EMT) and apoptosis in BC are not fully understood. We find that DNER is overexpressed in BC tissue, especially triple-negative breast cancer (TNBC) tissue, and related to the survival of BC and TNBC patients. In addition, DNER regulates cell EMT to enhance the proliferation and metastasis of BC cells via the Wnt/β-catenin pathway in vitro and in vivo. Moreover, the expression levels of β-catenin and DNER in BD tissue are positively correlated. The simultaneously high expression of DNER and β-catenin contributes to poor prognosis in BC patients. Finally, DNER protects BC cells from epirubicin-induced growth inhibition and apoptosis via the Wnt/β-catenin pathway. In conclusion, these results suggest that DNER induces EMT and prevents apoptosis by the Wnt/β-catenin pathway, ultimately promoting the malignant progression of BC. In conclusion, our study demonstrates that DNER functions as an oncogene and potentially valuable therapeutic target for BC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • China
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Membrane Proteins / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oncogenes
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / metabolism


  • CTNNB1 protein, human
  • DNER protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • beta Catenin