PXD038859

PXD038859 is an original dataset announced via ProteomeXchange.

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

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.

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]

submitter keyword: Protein degradation, PROTAC, Tyrosine kinase, FER, Ovarian cancer

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

iProX dataset URI