ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance

Cell Cycle. 2015;14(4):481-7. doi: 10.1080/15384101.2015.1006048.


Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that promotes tumor invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) in carcinoma cells. EMT not only plays an important role in embryonic development and malignant progression, but is also implicated in cancer therapy resistance. It has been hypothesized that carcinoma cells that have undergone EMT acquire cancer stem cell properties including self-renewal, chemoresistance and radioresistance. However, our recent data indicate that ZEB1 regulates radioresistance in breast cancer cells through an EMT-independent mechanism. In this Perspective, we review different mechanisms by which ZEB1 regulates tumor progression and treatment resistance. Based on studies by us and others, we propose that it is specific EMT inducers like ZEB1, but not the epithelial or mesenchymal state itself, that dictate cancer stem cell properties.

Keywords: ZEB1; drug resistance; epithelial-mesenchymal transition; metastasis; radioresistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epithelial-Mesenchymal Transition / physiology*
  • Homeodomain Proteins / physiology*
  • Humans
  • Models, Biological
  • Neoplasm Metastasis / physiopathology*
  • Neoplasms / physiopathology*
  • Neoplasms / radiotherapy
  • Radiation Tolerance / physiology*
  • Transcription Factors / physiology*
  • Zinc Finger E-box-Binding Homeobox 1


  • Homeodomain Proteins
  • Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1