Journal: Cancer Drug Resistance
Article Title: ZEB2 upregulation modulates the polarization of TAMs toward the immunosuppressive state in EGFR-TKI-resistant NSCLC
doi: 10.20517/cdr.2024.206
Figure Lengend Snippet: ZEB2 expression was regulated via the PI3K-Akt pathway in EGFR-TKI-resistant NSCLC. (A) The PI3K-Akt and MAPK signaling pathways were among the most significantly upregulated downstream pathways after EGFR-TKI resistance development in HCC827 and HCC4006 NSCLC cell lines. Common upregulated DEGs of these two cell lines before and after erlotinib resistance were included in this KEGG analysis; (B) The correlation between ZEB2 and key biomarkers of the PI3K-Akt [Akt1(R = 0.203), Akt2(R = 0.173), Akt3(R = 0.609)], MAPK [MAPK(R = 0.314), MAPK8(R = 0.091), MAPK14(R = 0.345)], and NF-κB signaling pathways [NF-κB(R = 0.482), p65(R = 0.169)] were assessed in the LUAD cohort from the TCGA database; (C) Western blotting was conducted to detect the phosphorylation level of key modulators of the PI3K-Akt, MAPK, and NF-κB signaling pathways before and after EGFR-TKI resistance in PC9 and HCC827 cells; (D-F) After 72 h of intervention with gradient concentrations of specific inhibitors of Akt(MK2206), ERK(U0126), and NF-κB(PDTC), western blotting was performed to determine the expression of ZEB2 in PC9-GR and HCC827-GR cells. Representative protein bands and the average results from 3 independent experiments are shown. *** P < 0.0005, **** P < 0.0001.
Article Snippet: To assess the activation of the PI3K-Akt, MAPK, and NF-κB signaling pathways, AKT1/2/3 inhibitor MK2206 (MedChemExpress, HY10358), ERK 1/2 inhibitor U0126 (MedChemExpress, HY12031A), and NF-κB inhibitor PDTC (MedChemExpress, HY18738) were used respectively on resistant NSCLC cells for 72 h. Then, the mRNA and protein of these cells were harvested for the following experiments.
Techniques: Expressing, Protein-Protein interactions, Western Blot, Phospho-proteomics
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![ZEB2 expression was regulated via the PI3K-Akt pathway in EGFR-TKI-resistant NSCLC. (A) The PI3K-Akt and MAPK signaling pathways were among the most significantly upregulated downstream pathways after EGFR-TKI resistance development in HCC827 and HCC4006 NSCLC cell lines. Common upregulated DEGs of these two cell lines before and after erlotinib resistance were included in this KEGG analysis; (B) The correlation between ZEB2 and key biomarkers of the PI3K-Akt <t>[Akt1(R</t> = 0.203), Akt2(R = 0.173), Akt3(R = 0.609)], MAPK [MAPK(R = 0.314), MAPK8(R = 0.091), MAPK14(R = 0.345)], and NF-κB signaling pathways [NF-κB(R = 0.482), p65(R = 0.169)] were assessed in the LUAD cohort from the TCGA database; (C) Western blotting was conducted to detect the phosphorylation level of key modulators of the PI3K-Akt, MAPK, and NF-κB signaling pathways before and after EGFR-TKI resistance in PC9 and HCC827 cells; (D-F) After 72 h of intervention with gradient concentrations of specific inhibitors of <t>Akt(MK2206),</t> ERK(U0126), and NF-κB(PDTC), western blotting was performed to determine the expression of ZEB2 in PC9-GR and HCC827-GR cells. Representative protein bands and the average results from 3 independent experiments are shown. *** P < 0.0005, **** P < 0.0001.](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_9605/pmc12159605/pmc12159605__cdr-8-25.fig.5.jpg)