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Cell Death & Disease

Cell Death & Disease

IF: 8.1
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CYP1B1 inhibits ferroptosis and induces anti-PD-1 resistance by degrading ACSL4 in colorectal cancer.

Published:14 April 2023 DOI: 10.1038/s41419-023-05803-2 PMID: 37059712
Congcong Chen, Yabing Yang, Yanguan Guo, Jiashuai He, Zuyang Chen, Shenghui Qiu, Yiran Zhang, Hui Ding, Jinghua Pan, Yunlong Pan

Abstract

Immune checkpoint blockade (ICB) is a promising treatment strategy for colorectal cancer (CRC) patients. However, most CRC patients do not response well to ICB therapy. Increasing evidence indicates that ferroptosis plays a critical role in immunotherapy. ICB efficacy may be enhanced by inducing tumor ferroptosis. Cytochrome P450 1B1 (CYP1B1) is a metabolic enzyme that participates in arachidonic acid metabolism. However, the role of CYP1B1 in ferroptosis remains unclear. In this study, we demonstrated that CYP1B1 derived 20-HETE activated the protein kinase C pathway to increase FBXO10 expression, which in turn promoted the ubiquitination and degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4), ultimately inducing tumor cells resistance to ferroptosis. Furthermore, inhibiting CYP1B1 sensitized tumor cells to anti-PD-1 antibody in a mouce model. In addition, CYP1B1 expression was negatively correlated with ACSL4 expression, and high expression indicates poor prognosis in CRC. Taken together, our work identified CYP1B1 as a potential biomarker for enhancing anti-PD-1 therapy in CRC.

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Procduct Name CAS Molecular Formula Supplier Price
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 286 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 286 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 286 suppliers $16.00-$2691.10
2-[1-[4-[2-(4-Chlorophenoxy)acetyl]-1-piperazinyl]ethyl]-3-(2-ethoxyphenyl)-4(3H)-Quinazolinone 571203-78-6 C30H31ClN4O4 286 suppliers $16.00-$2691.10

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