Figure 7 from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma
Year: 2024
Type: other
Abstract: Nuclear FAK regulation of MKP1 expression is associated with cisplatin resistance. A, KMF FAK-WT and FAK-NLS− cells were treated with increased concentrations of cisplatin (0, 10, or 20 μmol/L) for 12 hours and protein lysates were immunoblotted for GFP-FAK, MKP1, pERK, and total ERK. B, Image quantitation of pERK to total ERK ratio or MKP1 levels (FAK-WT set to 0) from two independent experiments described in A. Values are means ± SD (***, P < 0.001). C, KMF FAK-WT and FAK-NLS− cells were treated 20 μmol/L cisplatin (24 hours) under control (DMSO) or with MKP1 inhibitor (BCI-215, 1 μmol/L) addition. Protein lysates were immunoblotted for pERK and total ERK. D, Image quantitation of pERK to total ERK ratio from two independent experiments described in C. Values are means ± SD with FAK-WT control set to 1 (*, P < 0.05). E, KMF FAK-WT and FAK-NLS− cells were treated 20 μmol/L cisplatin (48 hours) as above with MKP1 inhibitor (BCI-215, 1 μmol/L) addition, and cell lysates were immunoblotted for caspase-3 and cleaved caspase-3. F, Determination of IC50 values to cisplatin KMF FAK-WT (green bars) and FAK-NLS− (blue bars) cells in the presence of MKP1 inhibitor (BCI-215, 1 μmol/L) or DMSO control as determined by alamarBlue cell viability assay. Values are means ± SD from three independent experiments (*, P < 0.05; **, P < 0.01; ***, P < 0.001). G, Kaplan–Meier curves from 949 HGSOC patient samples that received adjuvant carbo- or cisplatin-based chemotherapy. Plots show probability of relapse-free survival in months with tumors high (red) or low (black) for MKP1 mRNA (HR = 1.4, P = 0.0024). ns, not significant; WCL, whole-cell protein lysate.
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4405647397