Fig. 1: Zeb1 is important for increased ferroptosis sensitivity of mesenchymal cancer cells. | Nature Cell Biology

Fig. 1: Zeb1 is important for increased ferroptosis sensitivity of mesenchymal cancer cells.

From: Zeb1 mediates EMT/plasticity-associated ferroptosis sensitivity in cancer cells by regulating lipogenic enzyme expression and phospholipid composition

Fig. 1: Zeb1 is important for increased ferroptosis sensitivity of mesenchymal cancer cells.The alternative text for this image may have been generated using AI.

a, Representative immunofluorescence and immunoblots of KPC cells, classified according to an epithelial (KPCe), mixed (KPCmix) or mesenchymal (KPCm) phenotype. Relative viability and death rate treated with ML210 (46 h) ± 1 µM ferrostatin-1 (Fer-1). Data are mean ± s.e.m. from n = 3 independent experiments, two-way analysis of variance (ANOVA) (with multiple comparisons). Scale bar, 50 µm. b, High expression of Zeb1 correlates with sensitivity to ferroptosis inducers, and inversely to the EGFR inhibitor erlotinib. ML210 sensitivity correlates with high Zeb1 and low FSP1 expression. Plotted values are z-scored Pearson’s correlation coefficients; line, median; box, 25th to 75th percentile; whiskers, 2.5th and 97.5th percentile expansion, available from the CTRP database (https://portals.broadinstitute.org/ctrp.v2.1/). CRISPR–Cas9 essentiality screens (CERES) identify Zeb1 as an important gene in MDA-MB-231 cells (marked in red), which is among the most sensitive towards ferroptosis inducers. Plotted data were mined from Dependency Map (https://depmap.org/portal). c, Left, representative immunofluorescence and immunoblots of MDA-MB-231 shCtrl and shZeb1 cells. Right, relative viability after ML210 ± 1 µM Fer-1 treatment (72 h). Data are mean ± s.e.m. from n = 6 independent experiments (n = 4 for Fer-1 treatments), two-way ANOVA (with multiple comparisons). Scale bar, 50 µm. d, Relative tumour growth of MDA-MB-231 shCtrl and shZeb1 in zebrafish larvae, ±Fer-1 pretreatment. Data are mean ± s.e.m. from n = 39 shCtrl, n = 33 shCtrl + Fer-1, n = 36 shZeb1 ± Fer-1, ordinary one-way-ANOVA. e, Representative immunofluorescence and immunoblots in control or TGFβ-treated KPCmix cells. Relative viability after ML210 ± Fer-1 treatment (72 h). Data are mean ± s.e.m. from n = 3 independent experiments, two-way-ANOVA, scale bar, 50 µm. f, Representative immunofluorescence and immunoblots of H358 lung and BxPC3 pancreatic cancer cells, before (WT) and after resistance selection against the EGFR inhibitor erlotinib (Tarceva, TR) or the chemotherapeutic agent gemcitabine (Gemzar, GR). Relative cell viability measured 72 h after indicated treatments. Data are mean ± s.e.m. from n = 3 (H358) and n = 4 (BxPC3) independent experiments; two-way- ANOVA. Scale bar, 50 µm.

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