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; |
Keyword List
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
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD040200
- Label: PRIDE project
- Name: KK-LC-1 as a feasible therapeutic target to eliminate ALDH+ stem cells in triple negative breast cancer