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The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene

Benjamin D Rowland1, René Bernards, Daniel S Peeper

  • 1Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Nature Cell Biology
|October 26, 2005
PubMed

Insights

Krüppel-like factor 4 (KLF4) regulates cell proliferation and can act as a tumor suppressor or oncogene. KLF4

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Krüppel-like factor 4 (KLF4) is a transcription factor with dual roles in tumor suppression and oncogenesis.
  • Its function is context-dependent, influencing cell proliferation and senescence.

Purpose of the Study:

  • To identify genes that bypass RAS(V12)-induced senescence.
  • To elucidate the mechanisms underlying KLF4's context-dependent functions in cell transformation and tumor suppression.

Main Methods:

  • Functional genomic screening to identify genes involved in senescence bypass.
  • Analysis of KLF4's effect on cell proliferation, cell-cycle inhibitors (p21CIP1), and tumor suppressor p53.
  • Investigation of KLF4's direct action on the p53 promoter.

Main Results:

  • KLF4 inhibits proliferation in untransformed cells but its effect is bypassed by oncogenic RAS(V12) or cyclin-D1.
  • Inactivation of p21CIP1 neutralizes KLF4's cytostatic effect and promotes oncogenic transformation.
  • KLF4 suppresses p53 expression, promoting RAS(V12)-mediated transformation and resistance to apoptosis.

Conclusions:

  • KLF4 acts as a regulator of p53, with its oncogenic potential dependent on p21CIP1 status.
  • These findings explain the context-specific oncogenic or tumor-suppressive roles of KLF4.
  • KLF4 depletion in breast cancer cells restores p53 levels and induces apoptosis.

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