Activated cdc42-associated kinase is up-regulated in non-small-cell lung cancer and necessary for FGFR-mediated AKT activation

Mol Carcinog. 2016 May;55(5):853-63. doi: 10.1002/mc.22327. Epub 2015 May 6.

Abstract

Activated cdc42-associated tyrosine kinase 1 (ACK1) has been reported to be implicated in non-small-cell lung cancer (NSCLC). However, the expression pattern and biological functions of ACK1 in the progression of NSCLC are not fully understood. In this study, it was found that the expression of ACK1 was significantly up-regulated in NSCLC samples compared to their adjacent normal tissues. Meanwhile, the expression of ACK1 was inversely correlated with the survival of NSCLC patients. Moreover, in the biological function studies, ACK1 was further validated to promote the growth, migration, and metastasis of NSCLC cells in vitro and in vivo. Mechanistically, ACK1 bind with FGFR1 and was essential for the phosphorylation of AKT induced by FGF. Our study demonstrated that ACK1 played an oncogenic role in the progression of NSCLC and ACK1 might be a promising target for the treatment of NSCLC.

Keywords: ACK1; FGFR1; cell proliferation and migration; non-small-cell lung cancer.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Fibroblast Growth Factors / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism*
  • Survival Analysis
  • Up-Regulation*

Substances

  • Fibroblast Growth Factors
  • FGFR1 protein, human
  • Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • TNK2 protein, human
  • Proto-Oncogene Proteins c-akt