PXD040200

PXD040200 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	KK-LC-1 as a feasible therapeutic target to eliminate ALDH+ stem cells in triple negative breast cancer
Description	Failure to achieve complete elimination of triple negative breast cancer (TNBC) stem cells after adjuvant therapy is associated with poor outcomes. Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells (BCSCs), and its enzymatic activity regulates tumor stemness. Identifying upstream targets to control ALDH+ cells may facilitate TNBC tumor suppression. Here, we show that KK-LC-1 determines the stemness of TNBC ALDH+ cells via binding with FAT1 and subsequently promoting its ubiquitination and degradation. This compromised the Hippo pathway and led to nuclear translocation of YAP1 and ALDH1A1 transcription. These findings identified the KK-LC-1-FAT1-Hippo-ALDH1A1 pathway in TNBC ALDH+ cells as a therapeutic target. To reverse the malignancy due to KK-LC-1 expression, we employed a novel computational approach and discovered Z839878730 (Z8) as an small-molecule inhibitor which may disrupt KK-LC-1 and FAT1 binding. We demonstrate that Z8 suppressed TNBC tumor growth via a mechanism that reactivated the Hippo pathway and decreased TNBC ALDH+ cell stemness and viability.
HostingRepository	PRIDE
AnnounceDate	2024-10-04
AnnouncementXML	Submission_2024-10-04_01:48:57.478.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haonan Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-16 14:24:00	ID requested
1	2023-04-12 08:31:20	announced
⏵ 2	2024-10-04 01:48:58	announced	2024-10-04: Updated project metadata.

Publication List

Bu J, Zhang Y, Wu S, Li H, Sun L, Liu Y, Zhu X, Qiao X, Ma Q, Liu C, Niu N, Xue J, Chen G, Yang Y, Liu C, stem cells in triple negative breast cancer. Nat Commun, 14(1):2602(2023) [pubmed]
10.1038/s41467-023-38097-1;

Bu J, Zhang Y, Wu S, Li H, Sun L, Liu Y, Zhu X, Qiao X, Ma Q, Liu C, Niu N, Xue J, Chen G, Yang Y, Liu C, stem cells in triple negative breast cancer. Nat Commun, 14(1):2602(2023) [pubmed]

10.1038/s41467-023-38097-1;

Keyword List

submitter keyword: cancer stem cell, TNBC, Hippo signaling pathway,ALDH+ stemness, protein-protein inhibitor.

submitter keyword: cancer stem cell, TNBC, Hippo signaling pathway,ALDH+ stemness, protein-protein inhibitor.

Contact List

Caigang Liu
contact affiliation	Cancer Stem Cell and Translation Medicine Lab, Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110004, China
contact email	liucg@sj-hospital.org
lab head
Haonan Li
contact affiliation	School of Bioengineering, Dalian University of Technology
contact email	nancylee0416@126.com
dataset submitter

Full Dataset Link List

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/2023/04/PXD040200
PRIDE project URI

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/2023/04/PXD040200

PRIDE project URI

Repository Record List

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