文章：

SMYD3通过EZH2甲基化调控胃癌进展及巨噬细胞极化

SMYD3 regulates gastric cancer progression and macrophage polarization through EZH2 methylation 

原文发布日期：2022-09-20 

英文摘要：

SET and MYND domain-containing protein 3 (SMYD3), a known histone methyltransferase, was reported to regulate cancer pathogenesis. However, its role in gastric development and progression remains unclear. EZH2 methylation had been associated with cancer metastasis, but the EZH2 methylation status in gastric cancer (GC) is unknown. Here, we report that EZH2 K421 methylation was responsible for gastric cancer cell soft agar colony formation, in vivo metastasis, and macrophage polarization. Mechanically, we identified SMYD3 as the methyltransferase of EZH2 at K421 residue which accelerates EZH2 Ubiquitin proteasome degradation. Cell harboring non-methylated EZH2 mutants promotes gastric cancer cell metastasis. Taken together, our results showed that SMYD3-EZH2 axis restricts gastric cancer metastasis via integrating epigenetic signaling. 

摘要翻译： 

含有SET和MYND结构域的蛋白3（SMYD3）作为一种已知的组蛋白甲基转移酶，被报道可调控癌症发病机制。然而，其在胃部发育及癌变进程中的作用仍不明确。EZH2甲基化此前已被认为与癌症转移相关，但EZH2在胃癌中的甲基化状态尚未可知。本研究发现，EZH2 K421位点甲基化直接影响胃癌细胞的软琼脂集落形成能力、体内转移特性及巨噬细胞极化。从机制上，我们证实SMYD3是催化EZH2蛋白K421位点甲基化的甲基转移酶，该修饰会加速EZH2通过泛素蛋白酶体途径降解。携带非甲基化EZH2突变体的细胞会显著促进胃癌细胞转移。综上所述，我们的研究揭示了SMYD3-EZH2轴通过整合表观遗传信号通路抑制胃癌转移的分子机制。

原文链接：

SMYD3 regulates gastric cancer progression and macrophage polarization through EZH2 methylation