Science子刊：北京大学张宏权/于宇团队揭示巴豆酸抑制乳腺癌转移并促进免疫治疗响应的新机制

Core Viewpoint - Recent research indicates that crotonate, a short-chain fatty acid, has potential as a candidate drug for inhibiting breast cancer growth and metastasis by inducing specific modifications in the EZH2 protein, enhancing responses to immunotherapy [4][9]. Group 1: Research Findings - Crotonate suppresses breast cancer metastasis and promotes immunotherapy response through ACSS2-mediated EZH2-K348 crotonylation [3][4]. - The study reveals a new pathway where crotonate leads to the degradation of EZH2 protein via crotonylation at the K348 site, resulting in decreased levels of H3K27me3 [6][8]. - Compared to the EZH2 inhibitor tazemetostat, crotonate shows superior efficacy in inhibiting breast cancer metastasis [8]. Group 2: Mechanism of Action - Crotonate is metabolized to crotonyl-CoA, which then induces the crotonylation of EZH2, leading to its ubiquitin-mediated degradation [6][9]. - The mechanism involves the action of acetyltransferase p300, which catalyzes the formation of EZH2-K348cr, promoting the degradation of the modified EZH2 protein [6][8].