NOLC1 Suppresses Immuno-chemotherapy by Inhibiting p53-mediated Ferroptosis in Gastric Cancer DOI Open Access

Shengsheng Zhao,

Ji Lin,

Bingzi Zhu

et al.

Published: Dec. 24, 2024

Gastric cancer (GC) is one of the most malignant cancers, and cisplatin (Cis)-based chemotherapy remains main clinical treatment for GC. However, Cis resistance often occurs, largely limiting its therapeutic efficacy in tumors. Therefore, a better understanding drug mechanism could reveal new approaches improving GC efficacy. Here, we define integrative role nucleolar coiled-body phosphoprotein 1 (NOLC1), molecular chaperone that significantly upregulated tissues Cis-resistant cells. Knocking down NOLC1 increased sensitivity to by regulating ferroptosis. Mechanistically, binds p53 DNA binding domain (DBD), decreasing nuclear translocation stimulated suppressing transcriptional functions. Then, p53-mediated ferroptosis suppressed. Furthermore, silence promoted ferroptosis-induced immunogenic cell death (ICD) reprogrammed immunosuppressive tumor microenvironment, thereby increasing anti-programmed death-1 (PD-1) therapy plus Cis. The combination anti-PD-1 effectively inhibited growth without significant side effects. In summary, our findings targeting may be novel strategy increase combined with immune checkpoint inhibitor (ICI) therapy.

Language: Английский

NOLC1 Suppresses Immuno-chemotherapy by Inhibiting p53-mediated Ferroptosis in Gastric Cancer DOI Open Access

Shengsheng Zhao,

Ji Lin,

Bingzi Zhu

et al.

Published: Dec. 24, 2024

Gastric cancer (GC) is one of the most malignant cancers, and cisplatin (Cis)-based chemotherapy remains main clinical treatment for GC. However, Cis resistance often occurs, largely limiting its therapeutic efficacy in tumors. Therefore, a better understanding drug mechanism could reveal new approaches improving GC efficacy. Here, we define integrative role nucleolar coiled-body phosphoprotein 1 (NOLC1), molecular chaperone that significantly upregulated tissues Cis-resistant cells. Knocking down NOLC1 increased sensitivity to by regulating ferroptosis. Mechanistically, binds p53 DNA binding domain (DBD), decreasing nuclear translocation stimulated suppressing transcriptional functions. Then, p53-mediated ferroptosis suppressed. Furthermore, silence promoted ferroptosis-induced immunogenic cell death (ICD) reprogrammed immunosuppressive tumor microenvironment, thereby increasing anti-programmed death-1 (PD-1) therapy plus Cis. The combination anti-PD-1 effectively inhibited growth without significant side effects. In summary, our findings targeting may be novel strategy increase combined with immune checkpoint inhibitor (ICI) therapy.

Language: Английский

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