AI Article Synopsis
- ARHGEF4 is a guanine nucleotide exchange factor that specifically activates Rac1 and Cdc42, and this study aimed to explore its impact on pancreatic cancer cell behavior.
- High levels of ARHGEF4 expression in pancreatic cancer samples were linked to poorer overall survival rates, suggesting it serves as a negative prognostic indicator.
- Suppressing ARHGEF4 reduced cell motility and invasiveness by affecting signaling pathways (ERK1/2 and GSK-3α/β), indicating that targeting ARHGEF4 could be a promising strategy for pancreatic cancer treatment.
Article 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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| http://dx.doi.org/10.3892/ijo.2018.4549 | DOI Listing |
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