GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis

Jeng Shou Chang, Chia Yi Su, Wen Hsuan Yu, Wei Jiunn Lee, Yu Peng Liu, Tsung Ching Lai, Yi Hua Jan, Yi Fang Yang, Chia Ning Shen, Jin Yuh Shew, Jean Lu, Chih Jen Yang, Ming Shyan Huang, Pei Jung Lu, Yuan Feng Lin, Min Liang Kuo, Kuo Tai Hua, Michael Hsiao

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

G-protein-coupled receptor kinase interacting protein 1 (GIT1) is participated in cell movement activation, which is a fundamental process during tissue development and cancer progression. GIT1/PIX forming a functional protein complex that contributes to Rac1/Cdc42 activation, resulting in increasing cell mobility. Although the importance of Rac1/Cdc42 activation is well documented in cancer aggressiveness, the clinical importance of GIT1 remains largely unknown. Here, we investigated the clinical significance of GIT1 expression in non-small-cell lung cancer (NSCLC) and also verified the importance of GIT1-Rac1/Cdc42 axis in stimulating NSCLC cell mobility. The result indicated higher GIT1 expression patients had significantly poorer prognoses in disease-free survival (DFS) and overall survival (OS) compared with lower GIT1 expression patients. Higher GIT1 expression was an independent prognostic factor by multivariate analysis and associated with migration/invasion of NSCLC cells in transwell assay. In vivo studies indicated that GIT1 promotes metastasis of NSCLC cells. Finally, GIT1 was found to stimulate migration/invasion by altering the activity of Rac1/Cdc42 in NSCLC cells. Together, the GIT1 expression is associated with poor prognosis in patients with NSCLC. GIT1 is critical for the invasiveness of NSCLC cells through stimulating the activity of Rac1/Cdc42.

Original languageEnglish
Pages (from-to)36278-36291
Number of pages14
JournalOncotarget
Volume6
Issue number34
DOIs
Publication statusPublished - 2015

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Keywords

  • GIT1
  • Lung cancer prognosis
  • Metastasis
  • Rac1/Cdc42
  • Rho GTPases

ASJC Scopus subject areas

  • Oncology

Cite this

Chang, J. S., Su, C. Y., Yu, W. H., Lee, W. J., Liu, Y. P., Lai, T. C., Jan, Y. H., Yang, Y. F., Shen, C. N., Shew, J. Y., Lu, J., Yang, C. J., Huang, M. S., Lu, P. J., Lin, Y. F., Kuo, M. L., Hua, K. T., & Hsiao, M. (2015). GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis. Oncotarget, 6(34), 36278-36291. https://doi.org/10.18632/oncotarget.5531