PXD048451-1

PXD048451 is an original dataset announced via ProteomeXchange.

Title	Treachery of hepatic protector triggers Notch signaling to promote hepatocyte-originated cholangiocarcinoma
Description	Here, we found mesencephalic astrocyte-derived neurotrophic factor (MANF), a hepatic protector, was upregulated in human ICC tissues and sleeping beauty transposon (SBT) or thioacetamide (TAA)-induced mice ICC tissues. We verified the oncogenic role of MANF in ICC using cell lines overexpressing/knocked down MANF and mice specifically knocked in/out MANF in hepatocytes. Lineage tracing revealed that MANF promoted mature hepatocytes transformation into ICC. Mechanistically, we found a complex composed of MANF, CK19, and Notch2 intracellular domain (NICD2). MANF interacted with CK19 at Ser35 to suppress CK19 phosphorylation and membrane recruitment. Cytosolic CK19 bound to AR domain of NICD2 to stabilize NICD2 protein level and trigger Notch signaling, which contributed to hepatocytes transformation to ICC. We uncover a novel role of MANF and the original mechanism，which shed light on ICC intervention and treatment.
HostingRepository	PRIDE
AnnounceDate	2025-08-25
AnnouncementXML	Submission_2025-08-24_16:04:24.093.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qiong Mei
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	2024-01-11 02:24:23	ID requested
⏵ 1	2025-08-24 16:04:24	announced

10.1038/s41418-025-01460-4;

Mei Q, Zhang Y, Li H, Ma W, Huang W, Wu Z, Huang Y, Liang Y, Wei C, Wang J, Ruan Y, Yang L, Huang Y, Shen Y, Liu J, Feng L, Shen Y, Hepatic factor MANF drives hepatocytes reprogramming by detaining cytosolic CK19 in intrahepatic cholangiocarcinoma. Cell Death Differ, 32(8):1441-1459(2025) [pubmed]

submitter keyword: Hepatocytes,IP-MS,Hucct1,Notch,Cholangiocarcinoma,CK19

Yuxian Shen
contact affiliation	School of Basic Medical Sciences, Anhui Medical University,
contact email	shenyx@ahmu.edu.cn
lab head
Qiong Mei
contact affiliation	School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China
contact email	qiongmeiah@163.com
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/2025/08/PXD048451

PRIDE project URI

• PRIDE
  1. PXD048451
     1. Label: PRIDE project
     2. Name: Treachery of hepatic protector triggers Notch signaling to promote hepatocyte-originated cholangiocarcinoma