Expression of cell cycle regulator cdk2ap1 suppresses tumor cell phenotype by non-cell-autonomous mechanisms

Oral Oncol. 2009 Sep;45(9):e106-12. doi: 10.1016/j.oraloncology.2009.05.001. Epub 2009 Jun 9.


We evaluated the effect of expressing the cell cycle regulator cdk2ap1 in epithelial or stromal cell compartments to reduce SCC growth in vitro and in vivo. Cell-autonomous and/or non-cell-autonomous expression of cdk2ap1 reduced tumor growth and invasion and altered cell cycle, adhesion, invasion, angiogenesis, and apoptotic gene expression, as assessed by several in vitro phenotype assays, quantitative real-time PCR, and in vivo molecular imaging using a novel three-way xenograft animal model. Our findings suggest that the interactions between cancer cells and fibroblasts that promote abnormal growth can be minimized by expressing cdk2ap1, supporting a novel concept by which tumor/growth suppressor genes can impact tumorigenesis phenotypes from non-cell-autonomous interactions within the tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Adhesion / physiology
  • Cell Communication / physiology
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Fibroblasts / metabolism
  • Humans
  • Mice
  • Neoplasm Invasiveness / prevention & control
  • Stromal Cells / metabolism
  • Tumor Suppressor Proteins / metabolism*


  • CDK2AP1 protein, human
  • Tumor Suppressor Proteins