Fig. 2: FAK/SRC promotes ferroptosis by upregulation of ACSL4.
From: FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression
A Knocking down of FAK results in downregulation of ACSL4 expression in HT1080 and B16-F10 cells. Western blot images confirm the expression of the indicated proteins. B FAK inhibitor defactinib treatment suppresses the expression of ACSL4 in HT1080 and B16-F10 cells. Western blot images confirm the expression of the indicated proteins. defactinib (20 μM for 12 h). C Overexpression of FAK promotes the expression of ACSL4 in HT1080 cells and B16-F10 cells. Western blot images confirm the expression of the indicated proteins. D Overexpression of ACSL4 restores the sensitivity to erastin induced lipid peroxidation and ferroptosis of FAK KD cells. Western blot images confirm the expression of the indicated proteins in indicated cells. Cells as indicated were treated with erastin (10 μM for HT1080 cells and 30 μM for B16-F10 cells) for 14 h for cell death measurement, or 12 h for lipid ROS measurement, cell death and lipid ROS were measured as described in Fig. 1A. E Knocking down of SRC results in downregulation of ACSL4 expression in HT1080 and B16-F10 cells. Western blot images confirm the expression of the indicated proteins. F SRC inhibitor saracatinib treatment suppresses the expression of ACSL4 in HT1080 and B16-F10 cells. Western blot images confirm the expression of the indicated proteins. saracatinib (40 μM for 12 h). G Overexpression of SRC promotes the expression of ACSL4 in HT1080 cells and B16-F10 cells. Western blot images confirm the expression of the indicated proteins. H Overexpression of ACSL4 restores the sensitivity to erastin induced lipid peroxidation and ferroptosis of SRC KD cells. Western blot images confirm the expression of the indicated proteins in indicated cells. Cells as indicated were treated with erastin (10 μM for HT1080 cells and 30 μM for B16-F10 cells) for 14 h for cell death measurement, or 12 h for lipid ROS measurement, cell death and lipid ROS were measured as described in Fig. 1A. Data are derived from three independent experiments, and each value represents the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, t test. (n = 3).
