Hyperphosphorylation of CDH1 in Glioblastoma Cancer Stem Cells Attenuates APC/C
Anaphase-Promoting Complex-Cyclosome
/ antagonists & inhibitors
Antigens, CD
/ genetics
Cadherins
/ antagonists & inhibitors
Carbamates
/ pharmacology
Cdc20 Proteins
/ genetics
Cell Cycle Proteins
/ genetics
Cell Survival
/ drug effects
Diamines
/ pharmacology
F-Box Proteins
/ genetics
Glioblastoma
/ drug therapy
Humans
Mitosis
/ drug effects
Neoplastic Stem Cells
/ drug effects
Phosphorylation
/ drug effects
Small Molecule Libraries
/ pharmacology
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
24
12
2018
revised:
07
03
2019
accepted:
24
04
2019
pubmed:
1
5
2019
medline:
2
5
2020
entrez:
1
5
2019
Statut:
ppublish
Résumé
Glioblastoma (GBM) is the most common and lethal primary brain tumor and remains incurable. This is in part due to the cellular heterogeneity within these tumors, which includes a subpopulation of treatment-resistant cells called cancer stem-like cells (CSC). We previously identified that the anaphase-promoting complex/cylosome (APC/C), a key cell-cycle regulator and tumor suppressor, had attenuated ligase activity in CSCs. Here, we assessed the mechanism of reduced activity, as well as the efficacy of pharmacologically targeting the APC/C in CSCs. We identified hyperphosphorylation of CDH1, but not pseudosubstrate inhibition by early mitotic inhibitor 1 (EMI1), as a major mechanism driving attenuated APC/C
Identifiants
pubmed: 31036696
pii: 1541-7786.MCR-18-1361
doi: 10.1158/1541-7786.MCR-18-1361
pmc: PMC7271747
mid: NIHMS1528287
doi:
Substances chimiques
Antigens, CD
0
CDH1 protein, human
0
Cadherins
0
Carbamates
0
Cdc20 Proteins
0
Cell Cycle Proteins
0
Diamines
0
F-Box Proteins
0
FBXO5 protein, human
0
Small Molecule Libraries
0
apcin
0
CDC20 protein, human
156288-95-8
Anaphase-Promoting Complex-Cyclosome
EC 2.3.2.27
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
1519-1530Subventions
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108743
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM112895
Pays : United States
Organisme : NIH HHS
ID : S10 OD023436
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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