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Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

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Cyclin-dependent kinase 2 (CDK2) is a key mediator for EGF-induced cell transformation mediated through the

C Peng1,2, W Zeng2, J Su2

  • 1The Hormel Institute, University of Minnesota, Austin, MN, USA.

Oncogene
|June 2, 2015
PubMed

Insights

Cyclin-dependent kinase 2 (CDK2) promotes cell transformation and c-fos expression. Targeting CDK2 and ELK4 may offer new strategies for skin cancer therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Cyclin-dependent kinase 2 (CDK2) regulates cell cycle transitions.
  • The role of CDK2 in tumorigenesis remains controversial, with some studies suggesting it is dispensable for proliferation.

Purpose of the Study:

  • To investigate the novel role of CDK2 in epidermal growth factor (EGF)-induced cell transformation.
  • To elucidate the underlying molecular mechanisms involving ELK4 and c-fos.

Main Methods:

  • Ectopic expression and knockdown of CDK2.
  • Ras (G12V)-induced foci formation assays.
  • Western blotting and quantitative real-time PCR to assess protein and gene expression.
  • Immunoprecipitation and in vitro kinase assays to study CDK2-ELK4 interaction.
  • Analysis of ELK4 and CDK2 expression in melanoma cell lines.

Main Results:

  • Ectopic CDK2 enhanced Ras-induced foci formation; CDK2 knockdown reduced EGF-induced cell transformation by downregulating c-fos.
  • CDK2 directly phosphorylates ELK4, regulating its transcriptional activity and c-fos expression.
  • ELK4 is overexpressed in melanoma, and knockdown of ELK4 or CDK2 attenuated melanoma cell malignancy.

Conclusions:

  • CDK2 plays a novel role in EGF-induced cell transformation through the ELK4/c-fos pathway.
  • CDK2 and ELK4 are potential molecular targets for skin cancer chemoprevention and therapy.

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