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. 2023 Jun 3;14(6):347. doi: 10.1038/s41419-023-05860-7

Fig. 7. The methionine metabolism-related positive feedback loop between SLC43A2 and NFκB signaling pathway promoted cell proliferation by inhibiting ferroptosis in ESCC.

Fig. 7

A, B The qRT-PCR assay was used to detect the mRNA expression level of SLC43A2 (A) and GPX4 (B) in ESCC cells treated with Bay 11-7082. n = 5 for each group, ***P < 0.001, two-tailed unpaired Student’s t test. C Western blot was used to detected the expression of SLC43A2, GPX4, p-IKKα/β (Ser176/180) and p-p65 (Ser536) in ESCC cells from (1) control+DMSO group; (2) MCR + DMSO group; (3) MCR + 30 μM + DMSO group; (4) MCR + 30 μM+Bay 11-7082 group, respectively. D The proliferation of ESCC cell from (1) control+DMSO group; (2) MCR + DMSO group; (3) MCR + 30 μM + DMSO group; (4) MCR + 30 μM+Bay 11-7082 group was detected by CCK-8 assay. n = 5 for each group, *P < 0.05, **P < 0.01, two-tailed unpaired Student’s t test, compared with the control group. E The colonies formation assay was performed to detect the proliferation of ESCC cells in (1) control+DMSO group; (2) MCR + DMSO group; (3) MCR + 30 μM + DMSO group; (4) MCR + 30 μM+Bay 11-7082 group. n = 5 for each group, *P < 0.05, **P < 0.01, ***P < 0.001, two-tailed unpaired Student’s t test. F, G The content of GSH and MDA in ECA109 (F) and EC9706 (G) in certain treatments were detected by ELISA in (1) control+DMSO group; (2) MCR + DMSO group; (3) MCR + 30 μM + DMSO group; (4) MCR + 30 μM+Bay 11-7082 group. n = 5 for each group, *P < 0.05, **P < 0.01, two-tailed unpaired Student’s t test. H The scheme diagram showed the regulating process. SLC43A2-mediated intake of methionine activated NFκB signaling pathway, which followed the increased expression of SLC43A2 and GPX4. Meanwhile, the increased intake of methionine upregulated the content of GSH in ESCC. The feedback loop between SLC43A2 and NFκB signaling pathway diminished the ferroptosis and promote tumor progression in ESCC. Data are presented as mean ± SD (n = 5).