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

23 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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Non-Small Cell Lung Carcinoma
Lung Neoplasms
Neoplasm Metastasis
G-Protein-Coupled Receptor Kinases
Receptor-Interacting Protein Serine-Threonine Kinases
Statistical Factor Analysis
Disease-Free Survival
Cell Movement
Neoplasms
Multivariate Analysis
Survival
Proteins

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis. / Chang, Jeng Shou; Su, Chia Yi; Yu, Wen Hsuan; Lee, Wei Jiunn; Liu, Yu Peng; Lai, Tsung Ching; Jan, Yi Hua; Yang, Yi Fang; Shen, Chia Ning; Shew, Jin Yuh; Lu, Jean; Yang, Chih Jen; Huang, Ming Shyan; Lu, Pei Jung; Lin, Yuan Feng; Kuo, Min Liang; Hua, Kuo Tai; Hsiao, Michael.

In: Oncotarget, Vol. 6, No. 34, 2015, p. 36278-36291.

Research output: Contribution to journalArticle

Chang, JS, Su, CY, Yu, WH, Lee, WJ, Liu, YP, Lai, TC, Jan, YH, Yang, YF, Shen, CN, Shew, JY, Lu, J, Yang, CJ, Huang, MS, Lu, PJ, Lin, YF, Kuo, ML, Hua, KT & Hsiao, M 2015, 'GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis', Oncotarget, vol. 6, no. 34, pp. 36278-36291. https://doi.org/10.18632/oncotarget.5531
Chang, Jeng Shou ; Su, Chia Yi ; Yu, Wen Hsuan ; Lee, Wei Jiunn ; Liu, Yu Peng ; Lai, Tsung Ching ; Jan, Yi Hua ; Yang, Yi Fang ; Shen, Chia Ning ; Shew, Jin Yuh ; Lu, Jean ; Yang, Chih Jen ; Huang, Ming Shyan ; Lu, Pei Jung ; Lin, Yuan Feng ; Kuo, Min Liang ; Hua, Kuo Tai ; Hsiao, Michael. / GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis. In: Oncotarget. 2015 ; Vol. 6, No. 34. pp. 36278-36291.
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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.",
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AU - Su, Chia Yi

AU - Yu, Wen Hsuan

AU - Lee, Wei Jiunn

AU - Liu, Yu Peng

AU - Lai, Tsung Ching

AU - Jan, Yi Hua

AU - Yang, Yi Fang

AU - Shen, Chia Ning

AU - Shew, Jin Yuh

AU - Lu, Jean

AU - Yang, Chih Jen

AU - Huang, Ming Shyan

AU - Lu, Pei Jung

AU - Lin, Yuan Feng

AU - Kuo, Min Liang

AU - Hua, Kuo Tai

AU - Hsiao, Michael

PY - 2015

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