Fig. 3.

MYC drives apoptotic priming and MCL1 dependency. a Heatmap of BH3 profiling showing sensitivity of human small cell lung cancer (SCLC) cell lines against specific apoptosis-inducing peptides. MYC expression in the individual cell lines is annotated on the left. b Sensitivity of SCLC cell lines toward apoptosis induction by sensitizer peptide MS1 as marker for MCL1-dependent apoptosis. Cell lines are grouped into MYC low and high expression. Sensitivity is calculated as area under the curve. Center line (median), lower/upper box hinges (25th/75th percentile), whiskers extend to the most extreme value within 1.5× interquartile range (IQR) of the hinges. c Cell viability screening of MYC (n = 4; GLC1, H82, H524, GLC2), MYCN (n = 3; GLC8, H69, SBC4), and MYCL (n = 4; H1092, H2029, CorL88, H889) amplified human SCLC cell lines treated with MCL1 inhibitor (S63845) for 72 h (n = 3). d GI₅₀ values SCLC cell lines treated with S63845. Cell lines are grouped according to their MYC status (n = 3). e GI₅₀ values of Myc paralog-activated CRISPRa cells treated with S63845. f Cell viability screening of MYC-amplified H82 and H524 cells ± BCL2 overexpression treated with S63845 (n = 3). g GI₅₀ values of cell viability screening in f (n = 3). h Relative cell viability of H82 (MYC-amplified) and H69 (MYCN-amplified) human SCLC cell lines 48 h after transfection with non-targeted small interfering RNA (siRNA) or siRNA directed against MCL1 (n = 3). i Western blot showing MCL1 and γH2AX levels in H82 (MYC-amplified) and H69 (MYCN-amplified) human SCLC cell lines 48 h after Ctrl. or MCL1 siRNA transfection. HSP90 was used as a loading control. Error bars indicate mean ± SEM. Two-tailed unpaired t tests, ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05. Source data are provided as a Source Data file