O-GlcNAc-induced nuclear translocation of hnRNP-K is associated with progression and metastasis of cholangiocarcinoma.
Bile Duct Neoplasms
/ metabolism
Biomarkers, Tumor
/ metabolism
Cell Line, Tumor
Cell Movement
Cell Nucleus
/ metabolism
Cell Proliferation
Cholangiocarcinoma
/ metabolism
Disease Progression
Female
Glucosamine
/ metabolism
Glycosylation
Heterogeneous-Nuclear Ribonucleoprotein K
/ metabolism
Humans
Male
Middle Aged
Multivariate Analysis
Neoplasm Invasiveness
Neoplasm Metastasis
Protein Transport
Treatment Outcome
O-GlcNAcylated proteins
bile duct cancer
heterogeneous nuclear ribonucleoprotein-K
metastasis
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
26
06
2018
revised:
06
10
2018
accepted:
03
11
2018
pubmed:
18
11
2018
medline:
18
12
2019
entrez:
17
11
2018
Statut:
ppublish
Résumé
O-GlcNAcylation is a key post-translational modification that modifies the functions of proteins. Associations between O-GlcNAcylation, shorter survival of cholangiocarcinoma (CCA) patients, and increased migration/invasion of CCA cell lines have been reported. However, the specific O-GlcNAcylated proteins (OGPs) that participate in promotion of CCA progression are poorly understood. OGPs were isolated from human CCA cell lines, KKU-213 and KKU-214, using a click chemistry-based enzymatic labeling system, identified using LC-MS/MS, and searched against an OGP database. From the proteomic analysis, a total of 21 OGPs related to cancer progression were identified, of which 12 have not been previously reported. Among these, hnRNP-K, a multifaceted RNA- and DNA-binding protein known as a pre-mRNA-binding protein, was one of the most abundantly expressed, suggesting its involvement in CCA progression. O-GlcNAcylation of hnRNP-K was further verified by anti-OGP/anti-hnRNP-K immunoprecipitations and sWGA pull-down assays. The perpetuation of CCA by hnRNP-K was evaluated using siRNA, which revealed modulation of cyclin D1, XIAP, EMT markers, and MMP2 and MMP7 expression. In native CCA cells, hnRNP-K was primarily localized in the nucleus; however, when O-GlcNAcylation was suppressed, hnRNP-K was retained in the cytoplasm. These data signify an association between nuclear accumulation of hnRNP-K and the migratory capabilities of CCA cells. In human CCA tissues, expression of nuclear hnRNP-K was positively correlated with high O-GlcNAcylation levels, metastatic stage, and shorter survival of CCA patients. This study demonstrates the significance of O-GlcNAcylation on the nuclear translocation of hnRNP-K and its impact on the progression of CCA.
Identifiants
pubmed: 30444036
doi: 10.1002/1878-0261.12406
pmc: PMC6360360
doi:
Substances chimiques
Biomarkers, Tumor
0
Heterogeneous-Nuclear Ribonucleoprotein K
0
Glucosamine
N08U5BOQ1K
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
338-357Subventions
Organisme : Thailand Research Fund and Medical Research Council-UK
ID : DBG5980004
Pays : International
Organisme : Post-Doctoral Training Program from Research Affairs and Graduate School, Khon Kaen University, Thailand
ID : 59151
Pays : International
Organisme : National Research University Grant, Khon Kaen University
ID : (NRU592009)
Pays : International
Organisme : US National Institutes of Health
ID : R01GM049077
Pays : International
Organisme : NIGMS NIH HHS
ID : R01 GM049077
Pays : United States
Informations de copyright
© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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