Fig. 8: The anti-ferroptosis effect of LAPTM4B could be universal in other types of cancer. | Cell Death & Disease

Fig. 8: The anti-ferroptosis effect of LAPTM4B could be universal in other types of cancer.

From: LAPTM4B counteracts ferroptosis via suppressing the ubiquitin-proteasome degradation of SLC7A11 in non-small cell lung cancer

Fig. 8

A Principal component analysis (PCA) of metabolomics profiling results in WT and KO A431, WT and KO Hela, and WT and KO PC3 cells. Three independent replicates are shown. B PCA plot of metabolomics profiling induced by LAPTM4B depletion within each individual cell line. C Selection of significantly perturbed metabolites by LAPTM4B depletion: 18 metabolites in A431 cells, 17 metabolites in Hela cells, and 21 metabolites in PC3 cells, after threshold (VIP > 1, p < 0.05) selection. D Union set of altered metabolites regulated by LAPTM4B among the three cell lines. E Heatmap displaying altered metabolites in LAPTM4B-depleted cell lines. F KEGG analysis of significantly altered pathways regulated by LAPTM4B in A431 cells (p < 0.05). G KEGG analysis of significantly altered pathways regulated by LAPTM4B in Hela cells (p < 0.05). H KEGG analysis of significantly altered pathways regulated by LAPTM4B in PC3 cells (p < 0.05). I KEGG analysis of significantly altered pathways regulated by LAPTM4B, based on the data intersection from A431, Hela, and PC3 cells (p < 0.05). J Circos plot was employed to visualize the metabolites and metabiotic progress regulated by LAPTM4B. K Measurement of malondialdehyde (MDA) in WT and LAPTM4B KO cells. Quantification of n = 4 experiments, mean ± SEM. Data normalized to “WT”. For A431 cells, p(WT, KO) = 0.003. For Hela cells, p(WT, KO) = 0.0045. For PC3 cells, p(WT, KO) = 0.0111. L Schematic diagram depicting the working model and the main findings in the current study, including the metabolic landscape regulated by LAPTM4B, the suppressive effect of LAPTM4B on cellular ferroptosis, and the protection of tumor cell growth from erastin-induced ferroptosis. These findings are supported by clinical patient samples and data mining of publicly available databases. The working model illustrates the detailed molecular mechanism, with LAPTM4B promoting SLC7A11 stability and protecting cells from ferroptosis through suppression of NEDD4L/ZRANB1-mediated proteasomal degradation. This mechanism stimulates NSCLC growth and progression.

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