三阴性乳腺癌
癌症研究
花生四烯酸
乳腺癌
磷脂酶A2
凝血酶
癌症
磷脂酶
医学
化学
酶
生物
内科学
生物化学
血小板
作者
Shuo Xu,Qing‐Zhang Tuo,Jie Meng,Xiaoni Wu,Changlong Li,Peng Lei
标识
DOI:10.1016/j.tranon.2023.101817
摘要
Ferroptosis is a recently identified form of regulated cell death that plays a crucial role in tumor suppression. In this study, we found that F2 (the gene encoding thrombin) was strongly upregulated in breast cancer (BRCA, TCGA Study Abbreviations) compared with normal samples and that lower F2 levels were associated with poorer prognosis in breast cancer patients. Thrombin induces ferroptosis in triple-negative breast cancer (TNBC) cells by activation of cytosolic phospholipase A2α (cPLA2α) activity to increase the release of arachidonic acid (AA). TNBC in all breast cancer subtypes exhibited the highest levels of PLA2G4A (the gene encoding cPLA2α) and Acsl4, and inhibition of cPLA2α and its downstream enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) reversed thrombin toxicity. In a mouse xenograft model of TNBC, thrombin treatment suppressed breast cancer growth which can be inhibited by ferroptosis inhibitor Liproxstatin-1 (Lip-1). Our study underscores the potential of the thrombin-ACSL4 axis as a promising therapeutic target for the treatment of TNBC.
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