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Palmitoylation of GPX4 via the targetable ZDHHC8 determines ferroptosis sensitivity and antitumor immunity

Nature Cancer volume 6, pages 768–785 (2025)Cite this article

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Abstract

Ferroptosis is closely linked with various pathophysiological processes, including aging, neurodegeneration, ischemia-reperfusion injury, viral infection and, notably, cancer progression; however, its post-translational regulatory mechanisms remain incompletely understood. Here we revealed a crucial role of S-palmitoylation in regulating ferroptosis through glutathione peroxidase 4 (GPX4), a pivotal enzyme that mitigates lipid peroxidation. We identified that zinc finger DHHC-domain containing protein 8 (zDHHC8), an S-acyltransferase that is highly expressed in multiple tumors, palmitoylates GPX4 at Cys75. Through small-molecule drug screening, we identified PF-670462, a zDHHC8-specific inhibitor that promotes the degradation of zDHHC8, consequently attenuating GPX4 palmitoylation and enhancing ferroptosis sensitivity. PF-670462 inhibition of zDHHC8 facilitates the CD8+ cytotoxic T cell-induced ferroptosis of tumor cells, thereby improving the efficacy of cancer immunotherapy in a B16-F10 xenograft model. Our findings reveal the prominent role of the zDHHC8–GPX4 axis in regulating ferroptosis and highlight the potential application of zDHHC8 inhibitors in anticancer therapy.

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Fig. 1: Small-molecule screening revealed that palmitoylation inhibitor 2-BP can increase the ferroptosis sensitivity of tumor cells.
Fig. 2: Palmitoylation of GPX4 is essential for ferroptosis resistance.
Fig. 3: zDHHC8 mediates GPX4 palmitoylation.
Fig. 4: ZDHHC8 deficiency increases the sensitivity of tumor cells to ferroptosis.
Fig. 5: zDHHC8-mediated GPX4 palmitoylation is negatively correlated with immune cell infiltration.
Fig. 6: PF-670462 increases ferroptosis sensitivity of tumor cells by targeting zDHHC8.
Fig. 7: PF-670462 inhibits immune escape of tumor through ferroptosis in vivo.

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Data availability

All data supporting the findings of this study are included in the paper and its supplementary files. The crystal structure of GPX4 used in this study is available from the Protein Data Bank (6hn3). The predicted structure of zDHHC8 was obtained from the AlphaFold Protein Structure Database (AF-Q9ULC8-F1). The predicted interaction between GPX4 and zDHHC8 was performed via HADDOCK2.4 (v.2.5; https://wenmr.science.uu.nl/haddock2.4/). The crystal structure of the GPX4 and zDHHC8 complex was extracted by PyMoL software v.2.5.2 (San Carlos). The human cancer data were derived from the TCGA Research Network (http://cancergenome.nih.gov/). Normal sample data were derived from the GTEx database (https://gtexportal.org/home/). Data of the immune infiltration analysis in SKCM, COAD and READ were obtained from TCGA Research Network and analyzed via the Tumor Immune Estimation Resource (https://cistrome.shinyapps.io/timer/). The whole-genome sequencing data of ZDHHC8-knockout HT-1080 cells generated in this study have been deposited in the Sequence Read Archive database under BioProject accession no. PRJNA1210772. Source data are provided with this paper.

Code availability

No unique code was developed for this study.

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Acknowledgements

We thank Y. Ao in Shenzhen University for providing the MEF cell line. This work was supported by the National Natural Science Foundation of China (82341047 to J.C. and 32170913 and 32370982 to B.H.), the Guangdong Basic and Applied Basic Research Foundation (2024B1515040009, 2023B1212060028 and 2023B1515120085 to J.C. and 2023B1515120083 to B.H.), the Guizhou Provincial Science and Technology Projects (Qian Kehe Basic-ZK (2024) General 594 to X.Z.), the Shenzhen Medical Research Fund (B2302008 to B.H.), Changzhou High-Level Health Talents Training Project (2022260 to F.Z.), Changzhou Science and Technology Project (CJ20230062 to F.Z.) and the Fundamental Research Funds for the Central Universities (23yxqntd001 to J.C.). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the paper.

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Authors and Affiliations

  1. MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, Innovation Center of the Sixth Affiliated Hospital, School of Life Sciences of Sun Yat-sen University, Guangzhou, China

    Liang Zhou, Guangyu Lian, Tao Zhou, Shuai Yang, Weining Li, Lilin Cheng, Jianru Lu, Qifeng Deng & Jun Cui

  2. Guangzhou Institute of Pediatrics, Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China

    Zhe Cai

  3. Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Ying Ye

  4. Department of Oncology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Mingfeng He

  5. Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China

    Bihui Huang

  6. Department of Gastrointestinal Surgery, The First People’s Hospital of Gui Yang, Gui Yang, China

    Xiaoqian Zhou

  7. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Cancer Research Center, Department of Pharmacology, Shenzhen University Medical School, Shenzhen, China

    Desheng Lu

  8. Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, China

    Feng Zhi

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  1. Liang Zhou
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  3. Tao Zhou
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Contributions

J.C. conceived the project and designed the experiments. L.Z. and G.L. performed the experiments. T.Z., Z.C., S.Y., W.L., L.C., Y.Y., M.H., J.L., Q.D., D.L., B.H., F.Z. and X.Z. provided technical help. L.Z. and G.L. analyzed the data. J.C. provided resources, and directed the research. L.Z., G.L. and J.C. wrote the paper. All authors read and approved the final paper.

Corresponding author

Correspondence to Jun Cui.

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Extended data

Extended Data Fig. 1 Inhibition of palmitoylation increases the ferroptosis sensitivity of various kind of tumor cells.

a, The cell viability of HT-1080 cells treated with RSL3 (0.05 μM) in conjunction with or without 2-BP (10 μM) and DFO (5 μM), Liproxstatin-1 (5 μM), Z-VAD-FMK (10 μM) or NSA (2.5 μM) for 24 h. b, Lactate dehydrogenase (LDH) release measurement of HT-1080 cells treated with RSL3 (0.05 μM) in conjunction with or without 2-BP (10 μM) and Ferrostatin-1 (Fer-1, 2 μM), DFO (5 μM), Liproxstatin-1 (5 μM), Z-VAD-FMK (10 μM) or NSA (2.5 μM) for 16 h. c, Images of HT-1080 cell colonies by crystal violet staining after treatment with the indicated concentrations of ML162 in conjunction with DMSO or 2-BP (10 μM) for 24 h. d, Propidium iodide (PI) incorporation measurement of HT-1080 cells treated with ML162 (0.05 μM) in combination with DMSO or 2-BP (10 μM) for 12 h. e, Lipid peroxidation assessment of HT-1080 cells treated with ML162 (0.05 μM) in conjunction with DMSO or 2-BP (10 μM) for 10 h. f, The cell viability of HT-1080 cells treated with the indicated concentrations of ML162 in conjunction with or without 2-BP (10 μM) and Ferrostatin-1 (Fer-1, 2 μM) for 24 h. g, Images of HT-1080 cell colonies by crystal violet staining after treatment with the indicated concentrations of IKE in conjunction with DMSO or 2-BP (10 μM) for 24 h. h, PI incorporation measurement of HT-1080 cells treated with IKE (1 μM) in combination with DMSO or 2-BP (10 μM) for 12 h. i, Lipid peroxidation assessment of HT-1080 cells treated with IKE (1 μM) in conjunction with DMSO or 2-BP (10 μM) for 10 h. j, The cell viability of HT-1080 cells treated with the indicated concentrations of IKE in conjunction with or without 2-BP (10 μM) and Fer-1 (2 μM) for 24 h. k, The cell viability of A375 cells treated with the indicated concentrations of RSL3 in conjunction with or without 2-BP (10 μM) and Fer-1 (2 μM) for 24 h. l-n, The cell viability of A375 (l), B16-F10 (m) and MC38 (n) cells treated with the indicated concentrations of ML162 in conjunction with or without 2-BP (10 μM) and Fer-1 (2 μM) for 24 h. Data in c and g are representative of three independent experiments. For b,d,e,h,i, data are presented as mean ± s.d. of n = 3 biological replicates per group. For a,f,j-n, data are presented as mean ± s.d. n = 4 biological replicates per group. Statistical analysis was performed using one-way ANOVA with Dunnett’s test (a,b), two-way ANOVA with Šídák’s test (d,e,h,i) and two-way ANOVA with Tukey’s test (f,j-n).

Source data

Extended Data Fig. 2 Inhibition of GPX4 palmitoylation increased the ferroptosis sensitivity of tumor cells.

a, Immunoblotting analysis of GPX4 palmitoylation by ABE assay in HEK293T cells transfected with plasmids encoding GPX4-HA for 36 h, followed with treatment of 2-BP (10 μM) for 12 h. b, HEK293T cells were transfected with plasmids encoding GPX4-HA for 36 h, followed with treatment of palmitic acid-azide (50 μM) with or without 2-BP (10 μM) for 8 h, then prepared for Click-iT reaction. c, Immunoblotting analysis of GPX4 palmitoylation by ABE assay after the treatment of DMSO, RSL3 (1 μM) or IKE (5 μM) for 10 h in HEK293T cells transfected with plasmid encoding GPX4-HA for 36 h. d, Immunoblotting analysis of GPX4 and Flag-FSP1 in indicated cell lines. e, Immunoblotting analysis of GPX4 in GPX4-KO HT-1080 cells overexpressing HA-tagged wild-type GPX4 or mutant GPX4-C75S. f, Schematic illustration of GPX4-competing peptides. g, Immunoblotting analysis of GPX4 palmitoylation by ABE assay in HT-1080 after the treatment of CPP-P Scr (10 μM), CPP-P Ctrl (10 μM) or CPP-P Comp (10 μM) for 12 h. h, Lipid peroxidation assessment of HT-1080 cells treated with IKE (1 μM) in conjunction with CPP-P Scr (10 μM), CPP-P Ctrl (10 μM) or CPP-P Comp (10 μM) for 10 h. i, The cell viability of HT-1080 cells treated with IKE (1 μM) in conjunction with CPP-P Scr (10 μM), CPP-P Ctrl (10 μM) or CPP-P Comp (10 μM), and Fer-1 (2 μM) for 24 h. j, Lipid peroxidation assessment of HT-1080 cells treated with IFN-γ (20 ng ml−1) and AA (20 μM) in conjunction with CPP-P Scr (10 μM), CPP-P Ctrl (10 μM) or CPP-P Comp (10 μM) for 36 h. k, The cell viability of HT-1080 cells treated with IFN-γ (20 ng ml-1) plus AA (20 μM) in conjunction with CPP-P Scr (10 μM), CPP-P Ctrl (10 μM) or CPP-P Comp (10 μM), and Fer-1 (2 μM) for 48 h. Data in d and e are representative of three independent experiments. For a–c,g, quantification of the indicated protein levels are determined by Image Lab software; data are presented as mean ± s.d. n = 3 independent experiments per group. For h,j, data are presented as mean ± s.d. of n = 3 biological replicates pe group. For i,k, data are presented as mean ± s.d. of n = 4 biological replicates per group. Statistical analysis was performed using two-tailed paired Student’s t-test (a,b), one-way ANOVA with Dunnett’s test (c,g) and two-way ANOVA with Tukey’s test (h-k); ns, not significant.

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Extended Data Fig. 3 zDHHC8 is required for GPX4 palmitoylation.

a,b, Immunoblotting analysis of GPX4 palmitoylation by ABE assay in HEK293T cells transfected with plasmids encoding indicated zDHHCs-Flag for 36 h. c, Immunoblotting analysis of zDHHC8 in mock or ZDHHC8-KO HT-1080 cells. d, Immunoblotting analysis of zDHHC8 in Zdhhc8-knockdown B16-F10 cells. e, The cell viability of mock or ZDHHC8-KO HT-1080 cells treated with RSL3 (0.05 μM) together with or without DFO (5 μM), Liproxstatin-1 (5 μM), Z-VAD-FMK (10 μM) or NSA (2.5 μM) for 24 h. f, LDH release measurement of mock or ZDHHC8-KO HT-1080 cells treated with RSL3 (0.05 μM) together with or without ferrostatin-1 (Fer-1, 2 μM), DFO (5 μM), Liproxstatin-1 (5 μM), Z-VAD-FMK (10 μM) or NSA (2.5 μM) for 16 h. g, Immunoblotting analysis of zDHHC8 in ZDHHC8-knockdown HT-1080 cells, MC38 cells and CRC derived organoid. h, The cell viability of shCtrl or shZDHHC8 HT-1080 cells treated with RSL3 (0.05 μM), ML162 (0.05 μM) or IKE (1 μM), together with or without Fer-1 (2 μM) for 24 h. i,j, The cell viability of Zdhhc8-knockdown (shZdhhc8) B16-F10 cells (i) and MC38 cells (j) treated with RSL3 (0.05 μM), ML162 (0.05 μM) or IKE (1 μM), together with or without Fer-1 (2 μM) for 24 h. k, The cell viability of mock or ZDHHC8-KO HT-1080 cells treated with the indicated concentrations of RSL3 (left) or ML162 (right) in conjunction with DMSO or 2-BP (10 μM) for 24 h. l, Relative GSH level of HT-1080 cells after treated with vehicle, IKE (1 μM) or indicated concentration of 2-BP for 12 h. Data in a-d,g are representative of three independent experiments. For e,h-k data are presented as mean ± s.d. of n = 4 biological replicates per group. For f,l, data are presented as mean ± s.d. of n = 3 biological replicates per group. Statistical analysis was performed using one-way ANOVA with Dunnett’s test (l) and two-way ANOVA with Tukey’s test (e,f,h-k); ns, not significant.

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Extended Data Fig. 4 ZDHHC8 deficiency inhibits colorectal cancer growth in vivo.

a, Analysis of mRNA expression of ZDHHC8 in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) using the Cancer Genome Atlas (TCGA) datasets. For COAD, n = 41 samples in normal tissues, and n = 458 samples in tumor tissues. For READ, n = 10 samples in normal tissues, and n = 166 samples in tumor tissues. b, ZDHHC8 mRNA expression level is negatively co-related with the infiltration of CD8+ T cells in COAD and READ based on TCGA database. c,d, mRNA and protein level of ZDHHC8 were detected by real-time PCR (c) or immunoblot analysis (d) in CRC patients. e, Immunoblotting analysis of GPX4 palmitoylation by ABE assay in CRC samples from patients. Adj, adjacent normal tissues; Ca, cancerous tissue. f, The cell viability of control (shCtrl) or Zdhhc8-knockdown (shZdhhc8) MC38 cells. g-i, Tumor images (g), tumor growth curve (h), and tumor weight (i) of shCtrl and shZdhhc8 MC38 subcutaneous tumors. j, Lipid peroxidation assessment of shCtrl and shZdhhc8 MC38 subcutaneous tumors. k, Flow cytometric analysis of CD8+ cells in shCtrl and shZdhhc8 MC38 subcutaneous tumors. l, Representative CD8α immunofluorescence staining images of MC38 tumor sections from shCtrl and shZdhhc8 groups (n = 6 mice per group, 2 sections per mouse). Scale bar, 50 μm. m-o, Flow cytometric analysis of IFNγ+ (m), TNF+ (n) and GZMB+ (o) CD8+ cytotoxic T cells in shCtrl and shZdhhc8 MC38 subcutaneous tumors. For a, the box represents the interquartile range (IQR). The central line indicates the median. The lower and upper bounds of the box represent the first quartile and the third quartile. The whiskers extend to the minima and maxima. Data points outside the range of the whiskers are considered outliers. For b, The Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/) accomplished the immune infiltration analysis, and the tumor purity adjusted the results. Spearman’s rank correlation test is used, following a two-sided test without adjustment for multiple comparisons. The partial correlation coefficient (part.cor) and the corresponding p value are shown on the plot. n = 458 tumor samples for COAD, n = 166 tumor samples for READ. For c, data are presented as mean ± s.d. of n = 30 samples in normal group and n = 42 samples in tumor group. For d, quantification of the indicated protein level is determined by Image Lab software; data are presented as mean ± s.d. n = 4 independent samples per group. For e, quantification of the indicated protein level is determined by Image Lab software; data are presented as mean ± s.d. n = 3 independent experiments per group. For f, data are presented as mean ± s.d. of n = 4 independent samples per group. For h-k,m-o, data are presented as mean ± s.d. of n = 6 mice in each group. Statistical analysis was performed using two-tailed paired Student’s t-test (e), two-tailed unpaired Student’s t-test (a,c,d), one-way ANOVA with Dunnett’s test (i-k,m-o) and two-way ANOVA with Tukey’s test (h).

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Extended Data Fig. 5 PF-670462 increases the ferroptosis sensitivity of tumor cells via zDHHC8-GPX4 axis.

a, The cell viability of HT-1080 cells treated with RSL3 (0.05 μM) in conjunction with or without PF-670462 (10 μM) and DFO (5 μM), Lipro-1 (5 μM), Z-VAD-FMK (10 μM) or NSA (2.5 μM) for 24 h. b, LDH release measurement of HT-1080 cells treated with RSL3 (0.05 μM) in conjunction with or without PF-670462 (10 μM) and Fer-1 (2 μM), DFO (5 μM), Lipro-1 (5 μM), Z-VAD-FMK (10 μM) or NSA (2.5 μM) for 16 h. c, The cell viability of HT-1080 cells treated with the indicated concentrations of ML162 or IKE in conjunction with or without PF-670642 (10 μM) and Fer-1 (2 μM) for 24 h. d, The cell viability of various tumor cells treated with the indicated concentrations of RSL3 with PF-670462 (10 μM) for 24 h. e,f, The cell viability of HT-1080 cells treated with the indicated concentrations of RSL3 with SR-3029 (e) or LH846 (f) for 24 h. g, Immunoblotting analysis of CK1ε and CK1δ in control (shCtrl) or CK1δ/ε-knockdown (shCK1δ/ε) HT-1080 cells. h, The cell viability of shCtrl and shCK1δ/ε HT-1080 cells after treatment with the indicated concentration of RSL3. i, Immunoblotting analysis of thermal stability of zDHHC8-Flag protein by CETSA after the treatment of DMSO, LH846 (10 μM) or PF-670462 (10 μM) in HEK293T cells transfected with plasmid encoding zDHHC8-Flag. j, Immunoblotting analysis of thermal stability of zDHHC8 (NTD)-Flag protein by CETSA after the treatment of DMSO or PF-670462 (10 μM) in HEK293T cells transfected with plasmid encoding zDHHC8 (NTD)-Flag. k, Immunoblotting analysis of thermal stability of zDHHC-Flag protein by CETSA after the treatment of DMSO or PF-670462 (10 μM) in HEK293T cells transfected with plasmid encoding zDHHC5-Flag, zDHHC9-Flag or zDHHC20-Flag. l, Real-time PCR analysis of ZDHHC8 mRNA level in HT-1080 cells treated with the indicated concentration of PF-670462 for 24 h. For a,c-f and h, data are presented as mean ± s.d. of n = 4 biological replicates per group. For b,l, data are presented as mean ± s.d. of n = 3 biological replicates per group. Data in g,i-k are representative of three independent experiments. For i, quantification of the indicated protein level is determined by Image Lab software; data are presented as mean ± s.d. n = 3 independent experiments per group. Statistical analysis was performed using one-way ANOVA with Dunnett’s test (a,b,l), two-way ANOVA with Šídák’s test (d) and two-way ANOVA with Tukey’s test (c,i); ns, not significant.

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Extended Data Fig. 6 PF-670462 selectively promotes zDHHC8 degradation.

Immunoblotting analysis of zDHHCs in HEK293T cells. HEK293T cells were transfected with plasmids encoding the indicated Flag-tagged zDHHCs for 24 h, then treated with the indicated concentrations of PF-670462 for 16 h. Cell lysates were harvested for immunoblotting analysis. Data are representative of three independent experiments.

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Extended Data Fig. 7 PF-670462 promotes lysosomal degradation of zDHHC8.

a, Immunoblotting analysis of zDHHC8-Flag in HEK293T cells. HEK293T cells were transfected with plasmid encoding zDHHC8-Flag for 24 h, then treated with PF-670462 (10 μM) for 8 h. Cycloheximide (CHX, 100 mg/mL) was added in all groups at the indicated time points. Cell lysates were harvested for immunoblotting analysis. b, Immunoblotting analysis of zDHHC8-Flag in HEK293T cells. HEK293T cells were transfected with plasmid encoding zDHHC8-Flag for 24 h. Then the cells were treated with MG132 (10 μM) or bafilomycin A1 (Baf A1, 20 nM) for 12 h, after the pre-treatment of PF-670462 (10 μM) for 8 h. c, Immunoblotting analysis of GPX4 palmitoylation by ABE assay in HEK293T cells transfected with plasmid encoding GPX4-HA for 36 h, then treated with PF-670462 (10 μM) for 12 h. d, Relative GSH level of HT-1080 cells after treated with IKE (1 μM) in combination with vehicle or PF-670462 (10 μM) for 10 h. For a–c, quantification of the indicated protein level is determined by Image Lab software; data are presented as mean ± s.d. n = 3 independent experiments per group. For d, data are presented as mean ± s.d. n = 3 independent experiments per group. Statistical analysis was performed using two-tailed paired Student’s t-test (c), one-way ANOVA with Dunnett’s test (b) and two-way ANOVA with Tukey’s test (a,d); ns, not significant.

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Extended Data Fig. 8 PF-670462 has no side cytotoxicity in vivo.

a, Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CR) and creatine kinase isoenzymes (CK-MB) level measurement from mice serum after the indicated treatment of PF-670462. b, Representative hematoxylin and eosin (H&E) staining in the mice tissues (heart, liver, spleen, lung and kidney) after the indicated treatment of PF-670462. Scale bar, 200 μm. Data in b are representative of three independent mice. For a, data are shown as mean ± s.d. of n = 3 mice in each group. Statistical analysis was performed using one-way ANOVA with Dunnett’s test (a); ns, not significant.

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Extended Data Fig. 9 PF-670462 enhances CD8+ T cell-mediated antitumor immunity.

a, Images of B16-F10 lung metastasis after treatment with vehicle or PF-670462 (10 mg/kg). b, Statistical of surface lung metastasis nodules. c, Hematoxylin-eosin (H&E) staining of B16-F10 metastasis lungs. Scale bar, 500 μm. d, The overall survival of B16-F10 lung metastasis model after treatment with vehicle and PF-670462 (10 mg/kg). n = 10 in each group. e, Tumor images of B16-F10 subcutaneous tumors in Rag2 -/- mice with indicated treatment. n = 5 in each group. f, Treatment schedule for replenishing of naïve CD8+ T cells and naïve B cells in Rag2 -/- mice. g, Tumor weight of B16-F10 subcutaneous tumors in Rag2 -/- mice with indicated treatment. n = 5 in each group. h. MEF-OVA cells were pretreated with PF-670462 (10 μM) for 6 h and then combinate with indicated concentrations of RSL3 for another 3 h, refresh the medium and the cell viability was detected after another 21 h culture. i, Treatment schedule of the vaccination model. j, The overall survival of B16-F10 subcutaneous tumor model with the indicated treatment. n = 12 mice in each group. For b, data are presented as mean ± s.d. of n = 6 mice in each group. For g, data are presented as mean ± s.d. of n = 5 mice in each group. For h, data are presented as mean ± s.d. of n = 3 biological replicates per group. Statistical analysis was performed using two-tailed unpaired Student’s t-test (b), two-way ANOVA with Šídák’s test (h), two-way ANOVA with Tukey’s test (g) and log-rank (Mantel–Cox) test (d,j); ns, not significant.

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Supplementary information

Supplementary Information

Supplementary Fig.1 and its legend.

Reporting Summary

Supplementary Tables 1–5

Supplementary Table 1. Clinical information of patients with melanoma and colorectal cancer. Supplementary Table 2. Primers used in this project. Supplementary Table 3. General information and inhibition effects of bioactive small-molecule compounds. Supplementary Table 4. General information and inhibition effects of AI-screening candidates. Supplementary Table 5. List of antibodies used in this project.

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Statistical source data

Statistical source data in all figures and extended data figures except for Extended Data Fig. 6.

Unprocessed western blots source data

Unprocessed western blots source data in Figs. 2, 3, 5 and 6 and Extended Data Figs. 2–7.

Fluorescent images source data

Fluorescent images source data in Figs. 1, 4, 5 and 7 and Extended Data Fig. 4.

High-resolution hematoxylin and eosin (H&E) images source data

High-resolution H&E staining images source data in Extended Data Figs. 8 and 9.

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Zhou, L., Lian, G., Zhou, T. et al. Palmitoylation of GPX4 via the targetable ZDHHC8 determines ferroptosis sensitivity and antitumor immunity. Nat Cancer 6, 768–785 (2025). https://doi.org/10.1038/s43018-025-00937-y

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