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Updated: Mar 15, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
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p27kip1 expression limits H-Ras-driven transformation and tumorigenesis by both canonical and non-canonical

Ilenia Pellizzari1, Linda Fabris1,2, Stefania Berton1

  • 1Division of Experimental Oncology 2, Department of Translational Research, CRO Aviano, National Cancer Institute, Aviano, Italy.

Oncotarget
|September 1, 2016
PubMed

Insights

The tumor suppressor p27Kip1 regulates Ras-induced cancer growth differently depending on the Ras type. It inhibits cell proliferation via CDK and stathmin interactions for H-Ras, but mainly via CDK for K-Ras.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The tumor suppressor p27Kip1 is crucial for controlling cell growth and metastasis.
  • Previous studies showed conflicting roles for p27Kip1 in Ras-induced transformation.
  • Our prior work indicated p27Kip1 regulates H-Ras activity through stathmin interaction.

Purpose of the Study:

  • To investigate the role of p27Kip1 in Ras-induced transformation.
  • To elucidate the distinct mechanisms by which p27Kip1 regulates H-Ras and K-Ras.
  • To validate findings in human cancer models.

Main Methods:

  • In vitro and in vivo experimental models.
  • Analysis of cell proliferation and tumor growth in Ras-transformed cells.
  • Assessment of Cyclin-Dependent Kinase (CDK) activity and stathmin-microtubule interactions.
  • Examination of human cancer cell lines and primary tumor samples.

Main Results:

  • p27Kip1 suppressed H-RasV12 cell proliferation and tumor growth by inhibiting CDK activity and stathmin's MT-destabilizing function.
  • In K-Ras4BV12 cells, p27Kip1 primarily acted in a CDK-dependent, stathmin-independent manner.
  • These findings were confirmed in human cancer models, including breast and sarcoma samples.

Conclusions:

  • p27Kip1 is a key regulator of Ras-induced transformation through distinct mechanisms.
  • A conserved pathway regulating H-Ras oncogenic activity exists from mouse to human.
  • This pathway holds potential therapeutic and diagnostic implications for anti-H-Ras therapies.
Keywords:
H-Ras and K-Rascell cycle progressionmetastasisp27kip1stathmin

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