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Article

ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer

  • Authors:
    • Keisuke Taniuchi
    • Mutsuo Furihata
    • Seiji Naganuma
    • Toshiji Saibara
  • View Affiliations / Copyright

    Affiliations: Departments of Endoscopic Diagnostics and Therapeutics, Kochi University, Nankoku, Kochi 783-8505, Japan, Departments of Pathology, Kochi University, Nankoku, Kochi 783-8505, Japan
  • Pages: 2224-2240
    |
    Published online on: August 31, 2018
       https://doi.org/10.3892/ijo.2018.4549
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Abstract

Rho guanine nucleotide exchange factor 4 (ARHGEF4) is a guanine nucleotide exchange factor that is specific for Rac1 and Cdc42. The aim of the present study was to investigate the role of ARHGEF4 in the motility and invasiveness of pancreatic cancer cells. Evaluation of an immunohistochemical staining of 102 resected pancreatic cancer samples demonstrated that high ARHGEF4 expression was correlated with an independent predictor of worse overall survival in univariate and multivariate analyses. Immunofluorescence analyses and Matrigel invasion assays demonstrated that suppression of ARHGEF4 inhibited the formation of membrane protrusions, and in turn inhibited cell motility and invasion. A phosphoprotein array analysis demonstrated that knockdown of ARHGEF4 decreased phosphorylated extracellular signal-regulated kinase (ERK)1/2 and glycogen synthase kinase-3 (GSK-3)α/β in pancreatic cancer cells, and ERK1/2 and GSK-3α/β were associated with ARHGEF4-related motility and invasiveness through an increase in cell protrusions. These results suggested that ARHGEF4 stimulates ERK1/2 and GSK-3α/β, and provided evidence that ARHGEF4 promotes cell motility and invasiveness. Inhibition of ARHGEF4 may be a novel approach to a targeted molecular therapy, as any such therapy would limit the motility and invasiveness of pancreatic cancer cells.
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Copy and paste a formatted citation
Spandidos Publications style
Taniuchi K, Furihata M, Naganuma S and Saibara T: ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer. Int J Oncol 53: 2224-2240, 2018.
APA
Taniuchi, K., Furihata, M., Naganuma, S., & Saibara, T. (2018). ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer. International Journal of Oncology, 53, 2224-2240. https://doi.org/10.3892/ijo.2018.4549
MLA
Taniuchi, K., Furihata, M., Naganuma, S., Saibara, T."ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer". International Journal of Oncology 53.5 (2018): 2224-2240.
Chicago
Taniuchi, K., Furihata, M., Naganuma, S., Saibara, T."ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer". International Journal of Oncology 53, no. 5 (2018): 2224-2240. https://doi.org/10.3892/ijo.2018.4549
Copy and paste a formatted citation
x
Spandidos Publications style
Taniuchi K, Furihata M, Naganuma S and Saibara T: ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer. Int J Oncol 53: 2224-2240, 2018.
APA
Taniuchi, K., Furihata, M., Naganuma, S., & Saibara, T. (2018). ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer. International Journal of Oncology, 53, 2224-2240. https://doi.org/10.3892/ijo.2018.4549
MLA
Taniuchi, K., Furihata, M., Naganuma, S., Saibara, T."ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer". International Journal of Oncology 53.5 (2018): 2224-2240.
Chicago
Taniuchi, K., Furihata, M., Naganuma, S., Saibara, T."ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer". International Journal of Oncology 53, no. 5 (2018): 2224-2240. https://doi.org/10.3892/ijo.2018.4549
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