Oxaliplatin reverses the GLP-1R-mediated promotion of intrahepatic cholangiocarcinoma by altering FoxO1 signaling.
epithelial-mesenchymal transformation
forkhead box O1
glucagon-like peptide-1
intrahepatic cholangiocarcinoma
oxaliplatin
Journal
Oncology letters
ISSN: 1792-1074
Titre abrégé: Oncol Lett
Pays: Greece
ID NLM: 101531236
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
11
05
2018
accepted:
25
04
2019
entrez:
20
8
2019
pubmed:
20
8
2019
medline:
20
8
2019
Statut:
ppublish
Résumé
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer, with a 5-year survival rate of <10%; effective drug treatment for ICC is currently lacking. Glucagon-like peptide-1 receptor (GLP-1R) is upregulated in ICC; however, the functions of GLP-1R in ICC remain unknown. In this study, the upregulation of GLP-1R was confirmed in ICC cells using reverse transcription-quantitative polymerase chain reaction and western blot analysis, and GLP-1R was determined to promote the migration and invasion of ICC cells using Transwell assays. This tumor-promoting effect depended on the upregulation of epithelial-mesenchymal transformation-associated proteins, which was mediated by the FoxO1 signaling pathway. It was also indicated that following oxaliplatin treatment, the effects of GLP-1R on EMT and invasion were reversed. This functional reversion was associated with the reduced phosphorylation of S256 in forkhead box O1 (FoxO1) and an increase in the levels of unphosphorylated FoxO1. These findings suggest that incretin-based therapies may increase the risk of ICC metastasis and should not be used solely for the treatment of patients with ICC.
Identifiants
pubmed: 31423269
doi: 10.3892/ol.2019.10497
pii: OL-0-0-10497
pmc: PMC6607039
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1989-1998Références
Diabetologia. 1999 Jul;42(7):856-64
pubmed: 10440129
Biochem J. 2001 Mar 15;354(Pt 3):605-12
pubmed: 11237865
Ann Surg. 2001 Oct;234(4):507-17; discussion 517-9
pubmed: 11573044
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
J Biol Chem. 2002 Nov 22;277(47):45276-84
pubmed: 12228231
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1649-54
pubmed: 15668399
Cell Metab. 2006 Mar;3(3):153-65
pubmed: 16517403
Oncogene. 2008 Apr 7;27(16):2276-88
pubmed: 18391970
Diabetes Metab. 2009 Apr;35(2):77-84
pubmed: 19251449
Nat Immunol. 2009 Oct;10(10):1057-63
pubmed: 19701188
Biochem Biophys Res Commun. 2009 Dec 18;390(3):585-90
pubmed: 19818731
N Engl J Med. 2010 Apr 8;362(14):1273-81
pubmed: 20375404
World J Gastrointest Oncol. 2010 Mar 15;2(3):136-45
pubmed: 21160821
Gastroenterology. 2011 Jul;141(1):150-6
pubmed: 21334333
Gastroenterology. 2011 Jul;141(1):20-3
pubmed: 21723985
Cell Death Dis. 2011 Jul 07;2:e179
pubmed: 21734725
PLoS One. 2011;6(9):e25166
pubmed: 21980390
J Natl Cancer Inst. 2012 Feb 8;104(3):228-39
pubmed: 22247021
PLoS One. 2012;7(2):e31394
pubmed: 22363635
Exp Diabetes Res. 2012;2012:635472
pubmed: 22577369
Cancer Cell. 2012 Jun 12;21(6):793-806
pubmed: 22698404
Toxicol In Vitro. 2012 Oct;26(7):1093-7
pubmed: 22819839
Hepatology. 2013 Feb;57(2):610-24
pubmed: 22911555
Nat Rev Cancer. 2013 Jul;13(7):482-95
pubmed: 23792361
Metabolism. 2014 Jan;63(1):9-19
pubmed: 24140094
Int J Mol Sci. 2013 Dec 13;14(12):24293-304
pubmed: 24351817
Cancer Cell. 2014 Feb 10;25(2):152-65
pubmed: 24525232
Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
pubmed: 24556840
Mol Biol Rep. 2014 Jul;41(7):4313-20
pubmed: 24577752
Diabetes Obes Metab. 2014 Sep;16(9):850-60
pubmed: 24641303
Metabolism. 2014 Sep;63(9):1141-8
pubmed: 25034387
Oncotarget. 2014 Sep 15;5(17):7820-32
pubmed: 25229838
Oncotarget. 2015 Feb 10;6(4):2349-65
pubmed: 25537512
CNS Neurol Disord Drug Targets. 2015;14(3):370-7
pubmed: 25544681
Cell Metab. 2015 Mar 3;21(3):379-91
pubmed: 25738454
Cancer Lett. 2015 Jul 28;363(2):137-45
pubmed: 25896630
Free Radic Biol Med. 2015 Nov;88(Pt B):108-146
pubmed: 26122708
Cancer Lett. 2015 Oct 28;367(2):129-37
pubmed: 26210254
Oncotarget. 2017 Jan 3;8(1):1703-1713
pubmed: 27924058
Cell Rep. 2016 Dec 13;17(11):2845-2856
pubmed: 27974199
Nat Rev Clin Oncol. 2017 Oct;14(10):611-629
pubmed: 28397828
J Clin Invest. 2017 Sep 1;127(9):3421-3440
pubmed: 28805661
Nat Rev Clin Oncol. 2018 Feb;15(2):95-111
pubmed: 28994423
Life Sci. 2018 Jan 15;193:124-131
pubmed: 29158051
J Clin Invest. 2017 Dec 1;127(12):4217-4227
pubmed: 29202475
Semin Cancer Biol. 2018 Jun;50:53-64
pubmed: 29309928
BMC Cancer. 2018 Jun 15;18(1):657
pubmed: 29907137
Diabetes. 1994 Apr;43(4):535-9
pubmed: 8138058