Basonuclin-1 modulates epithelial plasticity and TGF-β1-induced loss of epithelial cell integrity

Oncogene. 2015 Feb 26;34(9):1185-95. doi: 10.1038/onc.2014.54. Epub 2014 Mar 24.


Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine and critically involved in the progression of a variety of cancers. TGF-β1 signaling can impair tumor development by its anti-proliferative and pro-apoptotic features. In contrast, it may actively promote tumor progression and cancer cell dissemination by inducing a gradual switch from epithelial towards mesenchymal-like cell features (EMT-like), including decreased intercellular adhesion. Here, we show that expression of the transcription factor Basonuclin-1 (Bnc1) modulates TGF-β1-induced epithelial dedifferentiation of mammary epithelial cells. RNAi-mediated repression of Bnc1 resulted in enhanced intercellular adhesion and strongly impaired TGF-β1-dependent sheet disintegration and cell scattering. In contrast, forced expression of Bnc1 modifies plasma membrane/cytoskeletal dynamics and seemingly interferes with the initiation of sustainable cell-cell contacts. Follow-up analyses revealed that Bnc1 affects the expression of numerous TGF-β1-responsive genes including distinct EMT-related transcription factors, some of which modulate the expression of Bnc1 themselves. These results suggest that Bnc1 is part of a transcription factor network related to epithelial plasticity with reciprocal feedback-loop connections on which Smad-factors integrate TGF-β1 signaling. Our study demonstrates that Bnc1 regulates epithelial plasticity of mammary epithelial cells and influences outcome of TGF-β1 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Dedifferentiation
  • Cell Transformation, Neoplastic / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Mammary Glands, Human / metabolism*
  • Mammary Glands, Human / pathology
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta1 / metabolism*
  • Zinc Finger E-box-Binding Homeobox 1


  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Transcription Factors
  • Transforming Growth Factor beta1
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • BNC1 protein, human

Associated data

  • GEO/GSE54717