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PXD044011-1

PXD044011 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKeratin 19 is a component of CoREST linking transcriptional and epigenetic dysregulation in liver cancer
DescriptionPoor differentiation in cancer is often correlated with higher malignancy and treatment resistance. Dysregulated epigenetic modifications, such as histone acetylation levels, plays a key role in tumor differentiation, and serves as potential targets for treatment. In this report, through screening of transcription factors abnormally activated in HCC, we identified FOXP4, which promotes tumorigenesis through transactivation of KRT19. Remarkably, beyond a marker of stemness, KRT19 actively represses histone acetylation levels, resulting in transcriptional inhibition of differentiation regulators, such as HNF4A, thus promotes tumor malignancy. Mechanistically, KRT19 activates HDAC1 deacetylase by promoting assembly of the CoREST complex in the nucleus. Finally, HDAC inhibitor alone or in combination with lenvatinib specifically suppresses KRT19 and FOXP4 positive human and mouse liver tumors. These findings revealed transcriptional activation of a conditional component for histone deacetylase complex as a mechanism for modulation of epigenetic landscape in cancer, and unveils a new opportunity for targeted therapy.
HostingRepositoryiProX
AnnounceDate2023-07-22
AnnouncementXMLSubmission_2024-09-02_20:38:10.603.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterShixun Han
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQTRAP 6500+
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-07-23 20:17:45ID requested
12024-09-02 20:38:10announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Keratin 19, FOXP4, HDAC1, CoREST, deacetylation, liver cancer, HCC, differentiation, transcription factor, HDAC inhibitor
Contact List
Bin Zhao
contact affiliationLife Sciences Institute, Zhejiang University
contact emailbinzhao@zju.edu.cn
lab head
Shixun Han
contact affiliationLife Sciences Institute, Zhejiang University
contact emailsxhan@zju.edu.cn
dataset submitter
Full Dataset Link List
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