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Updated: Apr 12, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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Significance of KRAS/PAK1/Crk pathway in non-small cell lung cancer oncogenesis

Fariborz Mortazavi1,2,3, Jie Lu4, Ryan Phan5

  • 1Division of Hematology/Oncology, West Los Angeles VA, Los Angeles, CA, USA. fredmortazavi@ucla.edu.

BMC Cancer
|May 10, 2015
PubMed
Abstract

Insights

The KRAS/PAK1/Crk axis is crucial in non-small cell lung cancer (NSCLC) progression. Targeting this pathway with PAK1 inhibitors and prenylation inhibitors significantly impacts NSCLC cell behavior.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The key effectors driving mutated KRAS in lung cancer progression and metastasis remain unidentified.
  • This study investigates the role of the PAK1/Crk axis in transmitting oncogenic KRAS signals within non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • To elucidate the role of the PAK1/Crk axis in KRAS-driven oncogenesis in NSCLC.
  • To determine if proto-oncogene c-Crk acts as a KRAS effector in NSCLC.

Main Methods:

  • Immunohistochemistry was used on NSCLC specimens to correlate KRAS mutations with PAK1/Crk axis activation and adhesion molecule expression.
  • KRAS was inhibited in NSCLC cells using combined farnesyltransferase inhibitor (FTI) and geranylgeranyltransferase inhibitor (GGTI) to assess c-Crk's role.
  • NSCLC cell morphology, motility, and proliferation were examined after blocking the KRAS/PAK1/Crk axis with PAK1 inhibitors and prenylation inhibitors.

Main Results:

  • A negative correlation was observed between PAK1/Crk phosphorylation and E-cadherin/p120-catenin expression in NSCLC.
  • KRAS mutant tumors exhibited elevated p-PAK1(Thr423) levels compared to KRAS wild-type tumors.
  • Combined inhibition of PAK1 and KRAS effectors via prenylation inhibitors drastically altered NSCLC cell morphology, motility, and proliferation.

Conclusions:

  • Proto-oncogene c-Crk functions downstream of KRAS in NSCLC.
  • The KRAS/PAK1/Crk axis represents a significant pathway in the oncogenesis of KRAS-mutant lung cancer, highlighting its therapeutic potential.

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