Amlodipine inhibits Synaptotagmin-4's oncogenic activity on gastric cancer proliferation by targeting calcium signaling
文献类型：期刊论文
| 作者 | Huang, Wen4; Yang, Shuo2,3; Deng, Minying4; Luo, Rongkui4; Liang, Huaiyu4; Shen, Yanyan1; Yang, Biyu1; Xu, Chen4; Hou, Yingyong4 |
| 刊名 | FUNCTIONAL & INTEGRATIVE GENOMICS
 |
| 出版日期 | 2024-06-01 |
| 卷号 | 24期号:3页码:14 |
| 关键词 | Gastric cancer synaptotagmin-4 Calcium ion channel Mitogen-activated protein kinase signaling pathway Amlodipine |
| ISSN号 | 1438-793X |
| DOI | 10.1007/s10142-024-01345-8 |
| 通讯作者 | Xu, Chen(xuchen1251@yeah.net) ; Hou, Yingyong(houyingyong@hotmail.com) |
| 英文摘要 | Background: Gastric cancer (GC) remains a leading cause of cancer mortality globally. Synaptotagmin-4 (SYT4), a calcium-sensing synaptic vesicle protein, has been implicated in the oncogenesis of diverse malignancies. Purpose: This study delineates the role of SYT4 in modulating clinical outcomes and biological behaviors in GC. Methods: We evaluated SYT4 expression in GC specimens using bioinformatics analyses and immunohistochemistry. Functional assays included CCK8 proliferation tests, apoptosis assays via flow cytometry, confocal calcium imaging, and xenograft models. Western blotting elucidated MAPK pathway involvement. Additionally, we investigated the impact of the calcium channel blocker amlodipine on cellular dynamics and MAPK pathway activity. Results: SYT4 was higher in GC tissues, and the elevated SYT4 was significantly correlated with adverse prognosis. Both univariate and multivariate analyses confirmed SYT4 as an independent prognostic indicator for GC. Functionally, SYT4 promoted tumorigenesis by fostering cellular proliferation, inhibiting apoptosis, and enhancing intracellular Ca2+ influx, predominantly via MAPK pathway activation. Amlodipine pre-treatment attenuated SYT4-driven cell growth and potentiated apoptosis, corroborated by in vivo xenograft assessments. These effects were attributed to MAPK pathway suppression by amlodipine. Conclusion: SYT4 emerges as a potential prognostic biomarker and a pro-oncogenic mediator in GC through a Ca2+-dependent MAPK mechanism. Amlodipine demonstrates significant antitumor effects against SYT4-driven GC, positing its therapeutic promise. This study underscores the imperative of targeting calcium signaling in GC treatment strategies. |
| WOS关键词 | BETA-CELL MATURATION ; EXPRESSION ; CARCINOMA ; KINASE ; IV |
| 资助项目 | Shanghai Municipal Key Clinical Specialty Foundation |
| WOS研究方向 | Genetics & Heredity |
| 语种 | 英语 |
| WOS记录号 | WOS:001204810900002 |
| 出版者 | SPRINGER HEIDELBERG |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310626]  |
| 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.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Nantong Univ, Nantong Peoples Hosp 1, Affiliated Hosp 2, Dept Orthopaed, Nantong, Jiangsu, Peoples R China 3.Peoples Hosp Tongzhou Bay Demonstrat Zone, Dept Orthopaed, Nantong, Jiangsu, Peoples R China 4.Fudan Univ, Zhongshan Hosp, Dept Pathol, 180 Fenglin Rd, Shanghai 200032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, Wen,Yang, Shuo,Deng, Minying,et al. Amlodipine inhibits Synaptotagmin-4's oncogenic activity on gastric cancer proliferation by targeting calcium signaling[J]. FUNCTIONAL & INTEGRATIVE GENOMICS,2024,24(3):14. |
| APA | Huang, Wen.,Yang, Shuo.,Deng, Minying.,Luo, Rongkui.,Liang, Huaiyu.,...&Hou, Yingyong.(2024).Amlodipine inhibits Synaptotagmin-4's oncogenic activity on gastric cancer proliferation by targeting calcium signaling.FUNCTIONAL & INTEGRATIVE GENOMICS,24(3),14. |
| MLA | Huang, Wen,et al."Amlodipine inhibits Synaptotagmin-4's oncogenic activity on gastric cancer proliferation by targeting calcium signaling".FUNCTIONAL & INTEGRATIVE GENOMICS 24.3(2024):14. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。