Glucose-Dependent FOXM1 Promotes Epithelial-to-Mesenchymal Transition Via Cellular Metabolism and Targeting Snail in Human Pancreatic Cancer.
Cell Line, Tumor
Cell Movement
/ drug effects
Cells, Cultured
Claudin-1
/ genetics
Energy Metabolism
/ genetics
Epithelial Cells
/ drug effects
Epithelial-Mesenchymal Transition
/ genetics
Forkhead Box Protein M1
/ genetics
Gene Expression Regulation, Neoplastic
/ drug effects
Glucose
Humans
Mitochondria
/ drug effects
Pancreatic Ducts
/ cytology
Pancreatic Neoplasms
/ genetics
Snail Family Transcription Factors
/ genetics
Journal
Pancreas
ISSN: 1536-4828
Titre abrégé: Pancreas
Pays: United States
ID NLM: 8608542
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
pubmed:
6
2
2020
medline:
26
1
2021
entrez:
4
2
2020
Statut:
ppublish
Résumé
Transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in the progression of cancer including epithelial-to-mesenchymal transition (EMT). The aim of this study is to characterize the regulatory mechanisms of FOXM1 in EMT via pancreatic cancer metabolism. We investigated the regulation of EMT via mitochondrial respiration by FOXM1 using pancreatic cancer cell lines HPAC and PANC-1 and normal human pancreatic duct epithelial cells. Forkhead box protein M1 and Snail were strongly expressed in HPAC and PANC-1. Epithelial-to-mesenchymal transition-modulated claudin-1 level was lower in PANC-1 than in HPAC. In both cell lines in low-glucose medium, FOXM1 and Snail were decreased and claudin-1 was increased. Knockdown of FOXM1 increased claudin-1 and decreased Snail in both cell lines. Low-glucose medium and downregulation of FOXM1 inhibited the cell migration in both cell lines. In both cell lines, mitochondrial respiration was at higher levels in low-glucose medium than in high-glucose medium. Downregulation of FOXM1 induced mitochondrial respiration in high-glucose medium. In normal human pancreatic duct epithelial cells, FOXM1 and Snail were low and claudin-1 was highly expressed, whereas overexpression of FOXM1 decreased claudin-1. Glucose-dependent FOXM1 promoted EMT via Snail and pancreatic cancer metabolism.
Identifiants
pubmed: 32011531
doi: 10.1097/MPA.0000000000001485
pii: 00006676-202002000-00017
doi:
Substances chimiques
Claudin-1
0
FOXM1 protein, human
0
Forkhead Box Protein M1
0
Snail Family Transcription Factors
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
273-280Références
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