Fig. 8: A working model. | Cell Death & Disease

Fig. 8: A working model.

From: Inhibition of LSD1 induces ferroptosis through the ATF4-xCT pathway and shows enhanced anti-tumor effects with ferroptosis inducers in NSCLC

Fig. 8

Proposed working model of inhibiting LSD1 on ferroptosis in cancer cells. (Left) LSD1 enhances the demethylation of H3K9me2 at the ATF4 promoter and activates ATF4 expression, which leads to the upregulation of xCT, thereby inhibiting ferroptosis in cancer cells. (Right) Inhibition of LSD1 results in the gain of H3K9me2 at ATF4 promoters, which silences ATF4 gene expression, leading to the reduction of xCT and ferroptosis. In addition, the suppression of LSD1 leads to an increase in H3K4me2 levels at the promoter sequences of TFRC and ACSL4, which promotes the expression of TFRC and ACSL4, which will promote the synthesis of unsaturated fatty acid and the accumulation of intracellular iron, respectively, thus promoting ferroptosis.

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