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Development of the non-receptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness | |
2023-05 | |
发表期刊 | JOURNAL OF BIOLOGICAL CHEMISTRY (IF:4.0[JCR-2023],4.4[5-Year]) |
ISSN | 0021-9258 |
发表状态 | 已发表 |
DOI | 10.1016/j.jbc.2023.104825 |
摘要 | Aberrant overexpression of non-receptor tyrosine kinase FER has been reported in a variety of ovarian carcinoma-derived tumor cells and is a poor prognosis factor for patient survival. It plays an important role in tumor cell migration and invasion, acting concurrently in both kinase-dependent and -independent manners, which is not easily suppressed by conventional enzymatic inhibitors. Nevertheless, the proteolysis-targeting chimeras (PROTACs) technology offers a superior efficacy over conventional activity-based inhibitors by targeting both enzymatic and scaffold functions simultaneously. Hence in this study, we report the development of two PROTAC compounds that promote robust FER degradation in a cereblon-dependent manner. Both PROTAC degraders outperform an FDA-approved drug, Brigatinib, in ovarian cancer cell motility suppression. Importantly, these PROTAC compounds also degrade multiple oncogenic FER fusion proteins identified in human tumor samples. These results lay an experimental foundation to apply the PROTAC strategy to antagonize metastasis in ovarian and other types of cancers with aberrant expression of FER kinase and highlight PROTACs as a superior strategy for targeting proteins with multiple tumor-promoting functions. |
关键词 | Protein degradation PROTAC Tyrosine kinase FER Ovarian cancer |
收录类别 | SCI |
引用统计 | 正在获取...
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文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/331104 |
专题 | 生命科学与技术学院 生命科学与技术学院_PI研究组_范高峰组 生命科学与技术学院_硕士生 生命科学与技术学院_博士生 |
通讯作者 | Xiaobao Yang; Dake Li; Gaofeng Fan |
作者单位 | 1.School of Life Science and Technology, ShanghaiTech University, Shanghai, China 2.Gluetacs Therapeutics (Shanghai) Co., Ltd., Shanghai, China 3.Department of Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China |
第一作者单位 | 生命科学与技术学院 |
通讯作者单位 | 生命科学与技术学院 |
第一作者的第一单位 | 生命科学与技术学院 |
推荐引用方式 GB/T 7714 | Yanchun Zhang,Xuexue Xiong,Renhong Sun,et al. Development of the non-receptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2023. |
APA | Yanchun Zhang.,Xuexue Xiong.,Renhong Sun.,Xiaotong Zhu.,Chen Wang.,...&Gaofeng Fan.(2023).Development of the non-receptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness.JOURNAL OF BIOLOGICAL CHEMISTRY. |
MLA | Yanchun Zhang,et al."Development of the non-receptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness".JOURNAL OF BIOLOGICAL CHEMISTRY (2023). |
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