An Emerging Role for the Unfolded Protein Response in Pancreatic Cancer.
activating transcription factor 6 (ATF6)
endoplasmic reticulum (ER)
inositol-requiring enzyme 1 (IRE1)
protein kinase RNA-like ER kinase (PERK)
unfolded protein response (UPR)
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
12 Jan 2021
12 Jan 2021
Historique:
received:
14
12
2020
revised:
04
01
2021
accepted:
06
01
2021
entrez:
15
1
2021
pubmed:
16
1
2021
medline:
16
1
2021
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and one of the leading causes of cancer-associated deaths in the world. It is characterised by dismal response rates to conventional therapies. A major challenge in treatment strategies for PDAC is the presence of a dense stroma that surrounds the tumour cells, shielding them from treatment. This unique tumour microenvironment is fuelled by paracrine signalling between pancreatic cancer cells and supporting stromal cell types including the pancreatic stellate cells (PSC). While our molecular understanding of PDAC is improving, there remains a vital need to develop effective, targeted treatments. The unfolded protein response (UPR) is an elaborate signalling network that governs the cellular response to perturbed protein homeostasis in the endoplasmic reticulum (ER) lumen. There is growing evidence that the UPR is constitutively active in PDAC and may contribute to the disease progression and the acquisition of resistance to therapy. Given the importance of the tumour microenvironment and cytokine signalling in PDAC, and an emerging role for the UPR in shaping the tumour microenvironment and in the regulation of cytokines in other cancer types, this review explores the importance of the UPR in PDAC biology and its potential as a therapeutic target in this disease.
Identifiants
pubmed: 33445669
pii: cancers13020261
doi: 10.3390/cancers13020261
pmc: PMC7828145
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : Science Foundation Ireland
ID : 18/SPP/3522
Pays : Ireland
Organisme : Science Foundation Ireland co-funded under European Regional Development Fund
ID : 13/RC/2073
Organisme : EU H2020 MCSA INSPIRED
ID : RISE -734749
Organisme : Canada Research Chairs Program
ID : to SL
Organisme : SFI Industry Fellowship
ID : 18/IF/6247
Références
Sci Signal. 2017 Jun 06;10(482):
pubmed: 28588081
Cell. 2007 Jun 29;129(7):1337-49
pubmed: 17604722
FEBS J. 2019 Jan;286(2):241-278
pubmed: 30027602
Pancreas. 2011 May;40(4):557-66
pubmed: 21499210
J Mol Med (Berl). 2005 Oct;83(10):795-805
pubmed: 15976918
Sci Rep. 2016 Dec 20;6:39342
pubmed: 27996033
Gastroenterology. 2011 Oct;141(4):1463-72
pubmed: 21704586
Science. 2006 Jul 7;313(5783):104-7
pubmed: 16825573
J Biol Chem. 2016 Jul 22;291(30):15830-40
pubmed: 27226638
Mol Oncol. 2018 Sep;12(9):1498-1512
pubmed: 29738634
J Hepatol. 2013 Jul;59(1):98-104
pubmed: 23485523
Oncotarget. 2016 Oct 4;7(40):65982-65992
pubmed: 27602757
Oncogene. 2017 Jun 1;36(22):3094-3103
pubmed: 27941872
Sci Signal. 2016 May 03;9(426):ra44
pubmed: 27141928
Nat Commun. 2019 Jan 15;10(1):224
pubmed: 30644389
Trends Immunol. 2007 Jul;28(7):299-307
pubmed: 17560169
J Biol Chem. 1996 Jul 26;271(30):18181-7
pubmed: 8663458
Hum Pathol. 2007 Oct;38(10):1547-52
pubmed: 17640713
Cancer. 2012 May 15;118(10):2674-81
pubmed: 21935914
Sci Rep. 2014 Aug 01;4:5911
pubmed: 25081383
Mol Cell. 2000 Dec;6(6):1355-64
pubmed: 11163209
Biochem Biophys Res Commun. 2015 Mar 6;458(2):341-6
pubmed: 25646691
J Neurochem. 2019 Feb;148(4):516-530
pubmed: 30520047
Oncogene. 2011 Jul 7;30(27):3049-61
pubmed: 21339733
Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6561-6
pubmed: 21464300
Mol Cell Biol. 2014 Oct;34(20):3911-25
pubmed: 25113558
Cell Death Dis. 2019 Aug 16;10(9):622
pubmed: 31417078
Cancer Res. 2001 Jan 15;61(2):550-5
pubmed: 11212248
Front Immunol. 2018 Mar 05;9:422
pubmed: 29556237
CA Cancer J Clin. 2020 Sep;70(5):375-403
pubmed: 32683683
Appl Immunohistochem Mol Morphol. 2012 Jul;20(4):381-5
pubmed: 22495374
Am J Transl Res. 2019 Feb 15;11(2):765-779
pubmed: 30899378
Cell Death Dis. 2019 Feb 12;10(2):132
pubmed: 30755605
J Clin Oncol. 2007 Jan 20;25(3):319-25
pubmed: 17235047
N Engl J Med. 2011 May 12;364(19):1817-25
pubmed: 21561347
Front Oncol. 2019 Aug 30;9:848
pubmed: 31544066
Mol Cell Biol. 2012 Dec;32(24):5129-39
pubmed: 23071091
Biochim Biophys Acta. 2013 Oct;1833(10):2165-75
pubmed: 23665047
EMBO Rep. 2016 Oct;17(10):1374-1395
pubmed: 27629041
Biochim Biophys Acta. 2016 Aug;1863(8):2115-23
pubmed: 27155082
J Cell Physiol. 2015 Jul;230(7):1413-20
pubmed: 25546813
Oncotarget. 2017 Sep 12;8(47):81776-81793
pubmed: 29137221
Int J Cancer. 2009 Feb 15;124(4):853-61
pubmed: 19035451
Oncotarget. 2014 Jul 15;5(13):4881-94
pubmed: 24952679
Int J Mol Med. 2014 Sep;34(3):772-81
pubmed: 24970676
Mol Cell. 2014 Sep 4;55(5):758-70
pubmed: 25087875
J Transl Med. 2018 Jul 9;16(1):190
pubmed: 29986726
Nat Rev Dis Primers. 2016 Apr 21;2:16022
pubmed: 27158978
J Clin Invest. 2012 Feb;122(2):639-53
pubmed: 22232209
BMC Cancer. 2019 Jun 17;19(1):596
pubmed: 31208372
Oncotarget. 2015 Oct 13;6(31):32154-60
pubmed: 26452217
Oncogene. 2017 Nov 30;36(48):6738-6746
pubmed: 28825721
Oncogene. 2009 Oct 8;28(40):3513-25
pubmed: 19633682
Exp Cell Res. 2017 Oct 1;359(1):76-85
pubmed: 28827060
Cell. 2001 Dec 28;107(7):881-91
pubmed: 11779464
Gastroenterology. 1998 Aug;115(2):421-32
pubmed: 9679048
J Cell Biol. 2018 Apr 2;217(4):1287-1301
pubmed: 29507125
Nat Chem Biol. 2019 Aug;15(8):764-775
pubmed: 31320759
Cancer Res. 2013 Oct 15;73(20):6359-74
pubmed: 24097820
J Cancer. 2020 Jan 14;11(6):1505-1515
pubmed: 32047557
Mol Cancer Ther. 2016 May;15(5):1043-52
pubmed: 26939701
Cancer Res. 2017 Oct 15;77(20):5503-5517
pubmed: 28811332
EMBO J. 1996 Jun 17;15(12):3028-39
pubmed: 8670804
Cell Rep. 2013 Apr 25;3(4):1279-92
pubmed: 23583182
Ann Pancreat Cancer. 2019 Jun;2:
pubmed: 31528855
Oncogene. 2013 May 16;32(20):2499-509
pubmed: 22945652
Oncotarget. 2016 Jun 14;7(24):36719-36732
pubmed: 27167341
Nature. 2016 Dec 1;540(7631):150
pubmed: 27706144
Cancer Lett. 2014 Apr 10;345(2):157-63
pubmed: 23879960
Cancer Res. 2008 Apr 1;68(7):2085-93
pubmed: 18381413
Pancreatology. 2010;10(2-3):186-93
pubmed: 20484957
Oncotarget. 2017 Apr 4;8(14):22625-22639
pubmed: 28186986
Dev Cell. 2002 Jul;3(1):99-111
pubmed: 12110171
Cancer Res. 2013 Mar 15;73(6):1993-2002
pubmed: 23333938
World J Gastroenterol. 2015 Mar 21;21(11):3157-65
pubmed: 25805920
Science. 2011 Nov 25;334(6059):1081-6
pubmed: 22116877
Nat Commun. 2018 Aug 15;9(1):3267
pubmed: 30111846
Biochim Biophys Acta Mol Cell Res. 2017 Apr;1864(4):655-665
pubmed: 28093214
Sci Rep. 2018 Aug 10;8(1):12000
pubmed: 30097594
Nat Commun. 2015 Nov 30;6:8859
pubmed: 26617336
EMBO Mol Med. 2015 Apr 11;7(6):788-801
pubmed: 25864123
Int J Surg. 2019 May;65:32-38
pubmed: 30902754
Am J Transplant. 2014 Jul;14(7):1552-61
pubmed: 24903305
Trends Cancer. 2017 May;3(5):336-346
pubmed: 28718411
Clin Cancer Res. 2010 Jun 1;16(11):2927-31
pubmed: 20484021
J Gastroenterol Hepatol. 2006 Oct;21 Suppl 3:S92-6
pubmed: 16958683
Int J Mol Sci. 2017 Jun 22;18(7):
pubmed: 28640192
EMBO J. 2003 Mar 3;22(5):1180-7
pubmed: 12606582
Cancer Cell. 2017 Aug 14;32(2):185-203.e13
pubmed: 28810144
Gastroenterology. 2017 May;152(6):1492-1506.e24
pubmed: 28126348
Proc Natl Acad Sci U S A. 2017 May 16;114(20):E4020-E4029
pubmed: 28461470
Science. 2018 Jun 15;360(6394):
pubmed: 29773669
J Cell Physiol. 2019 Nov;234(11):19702-19714
pubmed: 30953364
J Biol Chem. 2018 Jul 13;293(28):11143-11153
pubmed: 29853638
Elife. 2016 Feb 27;5:e10250
pubmed: 26920219
Am J Pathol. 2011 Nov;179(5):2601-10
pubmed: 21907693
Clin Cancer Res. 1999 Nov;5(11):3711-21
pubmed: 10589791
Cancers (Basel). 2019 Jan 25;11(2):
pubmed: 30691003
Pancreas. 2004 Oct;29(3):179-87
pubmed: 15367883
Gut. 2018 Mar;67(3):497-507
pubmed: 28077438
Nat Rev Gastroenterol Hepatol. 2011 Dec 20;9(2):77-87
pubmed: 22183185
PLoS One. 2015 Jun 19;10(6):e0130192
pubmed: 26091099
Mol Cancer Ther. 2017 Sep;16(9):1898-1908
pubmed: 28611107
Nature. 2002 Jan 3;415(6867):92-6
pubmed: 11780124
PLoS One. 2017 Aug 30;12(8):e0184110
pubmed: 28854261
Mol Cell. 2009 Sep 11;35(5):551-61
pubmed: 19748352
Curr Cancer Drug Targets. 2014;14(4):407-17
pubmed: 24575976
Sci Signal. 2020 Mar 24;13(624):
pubmed: 32209699
PLoS One. 2016 Feb 05;11(2):e0148999
pubmed: 26849807
Cell Metab. 2006 Sep;4(3):245-54
pubmed: 16950141
Front Physiol. 2012 Aug 28;3:344
pubmed: 22973234
Sci Rep. 2015 Nov 04;5:16067
pubmed: 26530532
Gut. 1998 Jul;43(1):128-33
pubmed: 9771417
BMC Cell Biol. 2007 Aug 29;8:38
pubmed: 17727724
Clin Cancer Res. 2008 Oct 1;14(19):5995-6004
pubmed: 18829478
J Exp Med. 1945 Mar 1;81(3):233-46
pubmed: 19871454