Inhibition of MEIS3 Generates Cetuximab Resistance through c-Met and Akt

Figure 1

(a) Based on the IC50 of cetuximab in 43 colon cancer cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, we selected SNU-C1, CL-34, and SW1417 as cetuximab-resistant cell lines and HT-155, HCC2998, and DiFi-09844799147 as cetuximab-sensitive cell lines. (b) The RNA expression profile in both cetuximab-sensitive and cetuximab-resistant cells was obtained, and genes with low expression in cetuximab-resistant cell lines were identified. (c) Pipeline of transfection of sgRNA library and drug selection. (d) NGS readout was used to quantify sgRNA. (e) mRNA from bulk tumor tissue was extracted from 17 cetuximab-sensitive and nine cetuximab-resistant patients, and expression of MEIS3 was identified by qPCR. (f) Bulk tumor tissue protein from eight cetuximab-sensitive and six cetuximab-resistant cell lines was extracted, and the expression of MEIS3 was detected by western blot (). (g) The relationship between the expression of MEIS3 and the overall survival rate of COAD patients in TCGA database.

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