PXD059539

PXD059539 is an original dataset announced via ProteomeXchange.

Title	FMNL2/SRC-mediated androgen receptor translocation into the nucleus promotes enzalutamide resistance of prostate cancer
Description	Enzalutamide, a second-generation androgen receptor (AR) antagonist, has represented the association with improved overall survival in men with prostate cancer (PCa). However, PCa patients receiving enzalutamide will eventually develop resistance through various mechanisms without effective regimens. Here, we observed a higher level of formin-like 2 (FMNL2) in enzalutamide-resistant PCa cells. Functionally, FMNL2 knockdown partially re-sensitized enzalutamide-resistant PCa cells. Mechanistically, FMNL2 directly interacted with SRC kinase through FMNL2-FH1 and SRC-SH3 domain, which induced AR translocation from the cytoplasm to the nucleus, resulting in increased expression of the AR-targeted genes and leading to resistance to enzalutamide. Consistently, SRC inhibitor dasatinib rescued enzalutamide sensitivity and inhibited the proliferation of enzalutamide-resistant cancer cells. Taken together, our findings demonstrate a substantial role for FMNL2/SRC interaction in the regulation of AR translocation, suggesting that targeting FMNL2-mediated SRC activation might be a potential therapeutic strategy for enzalutamide-resistant PCa, and dasatinib could be an option.
HostingRepository	PRIDE
AnnounceDate	2025-01-13
AnnouncementXML	Submission_2025-01-13_08:50:11.356.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jianpeng Yu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-08 00:46:19	ID requested
⏵ 1	2025-01-13 08:50:11	announced

Dataset with its publication pending

submitter keyword: AR,FMNL2,prostate cancer，enzalutamide resistance

zhiqun shang
contact affiliation	the second hospital of Tinajin medical university
contact email	zhiqun_shang@tmu.edu.cn
lab head
Jianpeng Yu
contact affiliation	The second hospital of Tianjin Medical univ
contact email	yujianpeng@tmu.edu.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD059539

PRIDE project URI

• PRIDE
  1. PXD059539
     1. Label: PRIDE project
     2. Name: FMNL2/SRC-mediated androgen receptor translocation into the nucleus promotes enzalutamide resistance of prostate cancer