机构：[1]Department of Gastrointestinal Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.华中科技大学同济医学院附属同济医院[2]Department of Protein Chemistry and Proteinomics Facility at Technology Center for Protein Sciences, Tsinghua University, Beijing 100084, China.[3]Department of Integrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute Sichuan Cancer Center, School of Medicine University of Electronic Science and Technology, Chengdu 610000, China.四川省肿瘤医院[4]Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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.
基金：
This work is supported by NSFC (No. 81773113 G.W.,
No. 81874186 J.H., and No. 81922053 G.W.) and the National Key Research and
Development Program of China (No. 2022YFA1105303 G.W.).
第一作者机构：[1]Department of Gastrointestinal Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Song Da,Hu Fuqing,Huang Changsheng,et al.Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis[J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2023,120(52):e2305684120.doi:10.1073/pnas.2305684120.
APA：
Song Da,Hu Fuqing,Huang Changsheng,Lan Jingqin,She Xiaowei...&Wang Guihua.(2023).Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,120,(52)
MLA：
Song Da,et al."Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 120..52(2023):e2305684120
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