Targeting GRB7/ERK/FOXM1 Signaling Pathway Impairs Aggressiveness of Ovarian Cancer Cells (original) (raw)
Figure 2
GRB7/ERK/FOXM1 was regulated in the same signaling axis.
(A) Treatment with U0126 (5 µM) showed a significant reduction in the expression of ERK phosphorylation accompanied with FOXM1 in ovarian cancer cells time dependently, whereas no change in GRB7 expression was found in A2780cp cells. (B) Treatment of Thiostrepton (20 µM) remarkably reduced the expression of FOXM1 only but no change in the expressions of GRB7 and ERK phosphorylation in A2780cp cells (left). Depletion of FOXM1 by siRNA knockdown did not alter the expression of GRB7 and ERK phosphorylation (right). C, siRNA scrambled control. si1, si2 and si3 siRNAs targeting three different regions of human FOXM1 and knockdown the expression of FOXM1 by 60%, 45% and 70% respectively. (C) Two out of four GRB7 shRNA constructs (sh1 and sh2) showed ∼70% knockdown of GRB7 accompanied with a reduction of ERK phosphorylation and FOXM1 expressions in OVCA433 cells. The scrambled control (NC) was used as negative control. (D) Enforced expression of GRB7 increased ERK phosphorylation and FOXM1. However, treatment with either U0126 (10 µM) or PD98059 (20 µM) could suppress the induced ERK phosphorylation and FOXM1 in A2780cp and OVCA433 ovarian cancer cells.