Fig. 3

ARHGEF39 (A39) promoted the expression of CyclinA2, Cyclin D1, and MMP2 by facilitating phosphorylation of the P38-ATF2 signaling pathway. a The levels of p-P38, p-ATF2, Cyclin A2, Cyclin D1, and MMP2 were elevated after transfection with A39 cDNA in A549 cells. (b) The levels of p-ATF2, Cyclin A2, Cyclin D1, and MMP2 were downregulated after A39 RNAi transfection in H460 cells. (c) The increasing levels of p-ATF2, Cyclin A2, Cyclin D1, and MMP2 caused by A39 overexpression were counteracted by incorporation of SB203580, a P38 phosphorylation inhibitor, into the growth media. d Representative images of the immunohistochemical staining results in mice xenografts; the expression levels of p-P38, p-ATF, Cyclin D1, MMP2, and Ki-67 were compared between A549-A39 cells and A549-vector cells. e–f In the colony formation assay, the increase in cell proliferation induced by A39 overexpression was reversed by adding SB203580. g–h Cell cycle analysis showing that SB203580 incorporation attenuated the effect of A39 overexpression on facilitating S phase arrest. i, k Wound healing and (j, l) Matrigel assays showing that inhibition of P38 phosphorylation using SB203580 abolished the increase in cancer cell migration and invasion induced by A39 overexpression. Data are shown as the mean ± SD from three independent experiments. *P < 0.05, **P < 0.01; scale bar = 50 μm