PXD044011-1

PXD044011 is an original dataset announced via ProteomeXchange.

Title	Keratin 19 is a component of CoREST linking transcriptional and epigenetic dysregulation in liver cancer
Description	Poor 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.
HostingRepository	iProX
AnnounceDate	2023-07-22
AnnouncementXML	Submission_2024-09-02_20:38:10.603.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shixun Han
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	QTRAP 6500+

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-23 20:17:45	ID requested
⏵ 1	2024-09-02 20:38:10	announced

Dataset with its publication pending

submitter keyword: Keratin 19, FOXP4, HDAC1, CoREST, deacetylation, liver cancer, HCC, differentiation, transcription factor, HDAC inhibitor

Bin Zhao
contact affiliation	Life Sciences Institute, Zhejiang University
contact email	binzhao@zju.edu.cn
lab head
Shixun Han
contact affiliation	Life Sciences Institute, Zhejiang University
contact email	sxhan@zju.edu.cn
dataset submitter

iProX dataset URI