Extended Data Fig. 1: A kinome CRISPR screen in the lenvatinib-resistant liver cancer cell line SNU449. | Nature

Extended Data Fig. 1: A kinome CRISPR screen in the lenvatinib-resistant liver cancer cell line SNU449.

From: EGFR activation limits the response of liver cancer to lenvatinib

Extended Data Fig. 1

a, Liver cancer cells are resistant to lenvatinib treatment in vitro. Short-term viability assay of liver cancer cell lines. Cells were treated with increasing concentrations of lenvatinib for 72 h, and cell viability was determined using CellTiter-Blue. Data are mean ± s.e.m. Cell lines with half-maximum inhibitory concentration (IC50) values < 5 μM are classed as relatively sensitive cells, whereas cell lines with IC50 > 5 μM are classed as relatively resistant cells. SNU449, JHH1, SNU182, PLC/PRF5, MHCC97H, HepG2, SNU398, Huh7 and Hep3B, n = 8; Huh6 and SK-Hep1, n = 7. b, Scatter plots of log10-transformed normalized read counts of independent biological replicates of GeCKO library lentiviral transductions with R2 values shown (n = 3). Replicates from triplicate transductions showed good correlation at the sgRNA level. T0, SNU449 cells after puromycin selection; Tuntreated, SNU449 cells cultured for 14 days without drug treatment; Ttreated, SNU449 cells cultured for 14 days with 10 μM lenvatinib. c, Fold change distribution of all gRNAs targeting essential genes or nonessential genes in three independent biological replicates. The sgRNAs for essential genes were strongly depleted relative to the sgRNAs targeting nonessential genes, highlighting the quality of the screen. ‘p’, 50 sgRNAs targeting 10 essential genes (red); ‘n’, 50 non-targeting control sgRNAs (blue); ‘x’, 5,860 sgRNAs targeting 504 human kinases (grey). d, Average log2-transformed fold change in each individual EGFR gRNA in the pooled CRISPR library (n = 3 independent experiments). Data are mean ± s.e.m. P values were determined by two-sided unpaired Student’s t-test

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