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Cytoplasmic p27

Olivier Calvayrac1, Ada Nowosad2, Stéphanie Cabantous1

  • 1Cancer Research Center of Toulouse (CRCT), INSERM U1037, CNRS ERL5294, University of Toulouse, Toulouse, France.

The Journal of Pathology
|September 13, 2018
PubMed

Insights

Cytoplasmic p27Kip1 promotes lung cancer by inhibiting the tumor suppressor RhoB. This interaction, identified in mouse models and human lung tumors, suggests p27 localization and RhoB levels are key prognostic markers for non-small cell lung carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The cell cycle inhibitor p27Kip1 (p27) typically acts as a tumor suppressor in the nucleus.
  • Cytoplasmic localization of p27 can promote tumorigenesis through poorly understood mechanisms, particularly in non-small cell lung carcinoma (NSCLC).
  • Oncogenic pathways like Ras and PI3K/AKT can trigger p27 relocalization to the cytoplasm.

Purpose of the Study:

  • To investigate the mechanisms by which cytoplasmic p27 contributes to the development of NSCLC.
  • To determine if p27's oncogenic role involves interactions with other tumor suppressor proteins.
  • To evaluate the prognostic significance of p27 localization and RhoB expression in NSCLC patients.

Main Methods:

  • Utilized genetically modified mouse models to assess the relationship between p27 and RhoB in lung tumorigenesis.
  • Performed molecular and genetic analyses to investigate p27-RhoB interactions.
  • Analyzed a cohort of human NSCLC patient tumors for p27 localization and RhoB expression.

Main Results:

  • Provided evidence that cytoplasmic p27's oncogenic activity is mediated by the inhibition of the tumor suppressor GTPase RhoB.
  • Observed that RhoB expression is lost in p27-deficient tumors but maintained in tumors with wild-type or non-inhibitory p27 mutants.
  • Found that cytoplasmic p27, RhoB expression, and decreased patient survival are significantly associated in NSCLC.

Conclusions:

  • Cytoplasmic p27 inhibits the tumor suppressor RhoB, contributing to NSCLC development.
  • p27 localization and RhoB expression levels serve as a powerful prognostic marker for NSCLC patients.
  • Targeting the p27-RhoB interaction may offer therapeutic strategies for NSCLC.
Keywords:
RhoBlung cancernon-small cell lung carcinomap27/Kip1transgenic mice

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