PSAT1 integrates ferroptosis resistance and immune evasion to drive hepatocellular carcinoma progression.

Elevated PSAT1 expression in hepatocellular carcinoma is linked to ferroptosis resistance and poor clinical outcomes, and PSAT1 promotes tumor growth by suppressing ferroptosis.

• Why it matters: The mechanisms connecting serine/glycine metabolism to ferroptosis resistance and immune escape in HCC are unclear, limiting targeted therapeutic strategies.
• What they did: The study used in vitro and in vivo functional assays to test PSAT1, showing PSAT1 suppresses ferroptosis via an HSPA5-mediated adaptive endoplasmic reticulum response and stabilizes BCLAF1 to enhance HSPA5 mRNA stability and translation.
• The result: PSAT1 also remodels the immune microenvironment by promoting M2 macrophage polarization and regulatory T cell infiltration through NRF2-driven CCL5 production, and PSAT1 inhibition with aminooxyacetic acid potentiated anti-PD-1 antitumor efficacy.