SYT4 Interacts with PSMC6 to Facilitate Malignant Progression in Gastric Carcinoma via Activating Wnt/β-catenin Signaling
文献类型：期刊论文
| 作者 | Huang, Wen2; Luo, Rongkui2; Wang, Huimei2,3,4; Yang, Shuo; Yu, Zixiang2; Liu, Yufeng2; Liang, Huaiyu2; Shen, Yanyan1; Zhang, Xiaolei2; Shen, Licheng2 |
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
 |
| 出版日期 | 2025 |
| 卷号 | 21期号:15页码:6775-6793 |
| 关键词 | synaptotagmin-4 (SYT4) gastric cancer PSMC6 Wnt/beta-catenin signaling pathway borussertib drug target |
| ISSN号 | 1449-2288 |
| DOI | 10.7150/ijbs.118672 |
| 通讯作者 | Xu, Chen(xu.chen@zs-hospital.sh.cn) ; Hou, Yingyong(yingyonghou@126.com) |
| 英文摘要 | Background: Gastric cancer (GC), a prevalent and life-threatening malignancy, poses significant challenges in diagnosis and prognosis due to its complex molecular pathogenesis. Identifying novel biomarkers and therapeutic targets is crucial for advancing treatment strategies and improving patient outcomes. This study investigates the role of synaptotagmin-4 (SYT4), recently identified as an oncogene, in GC development. Methods: We integrated proteomic and clinical analyses to evaluate SYT4 expression levels and their correlations with clinical features. Bioinformatic and clinicopathological assessments further validated SYT4's clinical relevance. Through comprehensive in vitro and in vivo experiments-including immunoprecipitation-mass spectrometry (IP-MS), co-immunoprecipitation (Co-IP), GST pull-down assays, and TOP/FOP luciferase reporter assays-we delineated SYT4's biological functions and interaction mechanisms. Additionally, we investigated the therapeutic potential of borussertib, a specific SYT4 inhibitor, in suppressing Results: SYT4 expression was significantly upregulated in GC tissues and strongly correlated with poor prognosis. Functionally, SYT4 drove cell proliferation, promoted cell cycle progression, and suppressed apoptosis in both cellular and animal models. Mechanistic investigations revealed that SYT4 directly interacts with PSMC6 via its C2B domain (amino acids 288-423), and stabilizes PSMC6 protein, thereby activating the Wnt/(3-catenin signaling pathway. Notably, borussertib, a targeted SYT4 inhibitor, markedly suppressed SYT4 activity, leading to attenuated GC progression. Conclusion: Our findings demonstrate that SYT4 is a critical driver of GC progression via activation of the Wnt/(3-catenin pathway. Moreover, we uncovered a novel mechanism by which borussertib selectively inhibits SYT4's oncogenic activity, providing compelling evidence for its therapeutic potential in gastric cancer treatment. |
| WOS关键词 | EXPRESSION |
| 资助项目 | National Key Clinical Specialty Discipline Construction Program of China[YWP2023-001] ; Shanghai Municipal Key Clinical Specialty Foundation[shslczdzk01302] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001622421300013 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322061]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Chen; Hou, Yingyong |
| 作者单位 | 1.Shanghai Inst Mat Med, Chinese Acad Sci, Shanghai 201203, Peoples R China 2.Fudan Univ, Zhongshan Hosp, Dept Pathol, 180 Fenglin Rd, Shanghai 200032, Peoples R China 3.Tongzhou Bay Peoples Hosp, Dept Orthopaed, Nantong 226000, Jiangsu, Peoples R China 4.Nantong Univ, Nantong Peoples Hosp 1, Affiliated Hosp 2, Dept Orthopaed, Nantong 226000, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Wen,Luo, Rongkui,Wang, Huimei,et al. SYT4 Interacts with PSMC6 to Facilitate Malignant Progression in Gastric Carcinoma via Activating Wnt/β-catenin Signaling[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2025,21(15):6775-6793. |
| APA | Huang, Wen.,Luo, Rongkui.,Wang, Huimei.,Yang, Shuo.,Yu, Zixiang.,...&Hou, Yingyong.(2025).SYT4 Interacts with PSMC6 to Facilitate Malignant Progression in Gastric Carcinoma via Activating Wnt/β-catenin Signaling.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,21(15),6775-6793. |
| MLA | Huang, Wen,et al."SYT4 Interacts with PSMC6 to Facilitate Malignant Progression in Gastric Carcinoma via Activating Wnt/β-catenin Signaling".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 21.15(2025):6775-6793. |
入库方式： OAI收割
来源：上海药物研究所
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