转移
癌症研究
RAC1
癌症
生物
组蛋白
组蛋白甲基转移酶
体内
结直肠癌
信号转导
细胞生物学
遗传学
基因
作者
Da Song,Fang Hu,Changsheng Huang,Jingqin Lan,Xiaowei She,Cheng Zhao,Hong Wu,Anyi Liu,Weier Qi,Yaqi Chen,Xuelai Luo,Yongdong Feng,Xun Yang,Chuan Xu,Junbo Hu,Guihua Wang
标识
DOI:10.1073/pnas.2305684120
摘要
Metastasis is a major cause of cancer therapy failure and mortality. However, targeting metastatic seeding and colonization remains a significant challenge. In this study, we identified NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, as being overexpressed in metastatic tumors. Our findings suggest that NSD2 overexpression enhances tumor metastasis both in vitro and in vivo. Further analysis revealed that NSD2 promotes tumor metastasis by activating Rac1 signaling. Mechanistically, NSD2 combines with and activates Tiam1 (T lymphoma invasion and metastasis 1) and promotes Rac1 signaling by methylating Tiam1 at K724. In vivo and in vitro studies revealed that Tiam1 K724 methylation could be a predictive factor for cancer prognosis and a potential target for metastasis inhibition. Furthermore, we have developed inhibitory peptide which was proved to inhibit tumor metastasis through blocking the interaction between NSD2 and Tiam1. Our results demonstrate that NSD2-methylated Tiam1 promotes Rac1 signaling and cancer metastasis. These results provide insights into the inhibition of tumor metastasis.
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