ERK2 regulates epithelial-to-mesenchymal plasticity through DOCK10-dependent Rac1/FoxO1 activation Academic Article uri icon


MeSH Major

  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms
  • Cell Movement
  • Drug Resistance, Neoplasm
  • Focal Adhesion Kinase 1
  • Melanoma
  • Multiprotein Complexes
  • Protein Kinase Inhibitors
  • Receptors, Somatomedin
  • Skin Neoplasms
  • TOR Serine-Threonine Kinases


  • ERK is a key coordinator of the epithelial-to-mesenchymal transition (EMT) in that a variety of EMT-inducing factors activate signaling pathways that converge on ERK to regulate EMT transcription programs. However, the mechanisms by which ERK controls the EMT program are not well understood. Through an analysis of the global changes of gene expression mediated by ERK2, we identified the transcription factor FoxO1 as a potential mediator of ERK2-induced EMT, and thus we investigated the mechanism by which ERK2 regulates FoxO1. Additionally, our analysis revealed that ERK2 induced the expression of Dock10, a Rac1/Cdc42 GEF, during EMT. We demonstrate that the activation of the Rac1/JNK signaling axis downstream of Dock10 leads to an increase in FoxO1 expression and EMT. Taken together, our study uncovers mechanisms by which epithelial cells acquire less proliferative but more migratory mesenchymal properties and reveals potential therapeutic targets for cancers evolving into a metastatic disease state.

publication date

  • February 19, 2019



  • Academic Article



  • eng

PubMed Central ID

  • PMC6386703

Digital Object Identifier (DOI)

  • 10.1073/pnas.1811923116

PubMed ID

  • 30728292

Additional Document Info

start page

  • 2967

end page

  • 2976


  • 116


  • 8