PXD038859
PXD038859 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Development of the non-receptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer metastasis |
Description | 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 |
HostingRepository | iProX |
AnnounceDate | 2022-12-15 |
AnnouncementXML | Submission_2024-02-03_20:33:58.121.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Yanchun Zhang |
SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF-X |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2022-12-15 03:01:23 | ID requested | |
1 | 2022-12-15 03:06:30 | announced | |
⏵ 2 | 2024-02-03 20:33:58 | announced | 2024-02-04: Update publication information. |
Publication List
Zhang Y, Xiong X, Sun R, Zhu X, Wang C, Jiang B, Yang X, Li D, Fan G, Development of the nonreceptor tyrosine kinase FER-targeting PROTACs as a potential strategy for antagonizing ovarian cancer cell motility and invasiveness. J Biol Chem, 299(6):104825(2023) [pubmed] |
Keyword List
submitter keyword: Protein degradation, PROTAC, Tyrosine kinase, FER, Ovarian cancer |
Contact List
Gaofeng Fan | |
---|---|
contact affiliation | ShanghaiTech University |
contact email | fangf@shanghaitech.edu.cn |
lab head | |
Yanchun Zhang | |
contact affiliation | ShanghaiTech University |
contact email | zhangych3@shanghaitech.edu.cn |
dataset submitter |
Full Dataset Link List
iProX dataset URI |