The complexity of integrins in cancer and new scopes for therapeutic targeting.
Cancer is a complex disease and progresses within a dynamically evolving extracellular matrix that controls virtually every aspect of the tumour and tumour-associated cells. Interactions with the extracellular microenvironment are predominately mediated by a family of cell-surface transmembrane receptors called integrins. Integrin-matrix engagement leads to the formation of adhesion plaques, consisting of signalling and adaptor proteins, at the plasma membrane that link the extracellular matrix to the regulation of the cell cytoskeleton. In this review, we will highlight exciting data that identify new roles for integrins and integrin-dependent signalling in cancer away from the plasma membrane, discuss the implications of integrin-dependent regulation of Met and ErbB2 growth factor receptors and highlight the role of specific integrins in different stages of cancer development including maintenance of cancer stem cells.
Turku Centre for Biotechnology, University of Turku, Tykistökatu 6, Turku 20520, Finland.
Hellyeh
H
Hamidi
Turku Centre for Biotechnology, University of Turku, Tykistökatu 6, Turku 20520, Finland.
Mika
M
Pietilä
Turku Centre for Biotechnology, University of Turku, Tykistökatu 6, Turku 20520, Finland.|Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland.
Johanna
J
Ivaska
D000818:Animals; D006801:Humans; D016023:Integrins / Q000502:physiology*; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D015398:Signal Transduction; D035703:Therapies, Investigational / Q000379:methods / Q000639:trends; D059016:Tumor Microenvironment / Q000502:physiology
D016023:Integrins
Curr Opin Cell Biol. 2006 Oct;18(5):524-32
16908128
Cancer Res. 2016 May 1;76(9):2513-24
26988988
Nat Med. 2016 Aug;22(8):851-60
27376576
Nat Cell Biol. 2016 May;18(5):491-503
27043085
Nat Cell Biol. 2013 Jul;15(7):807-17
23728425
Ann Oncol. 2015 Jan;26(1):132-40
25319061
Nat Commun. 2016 May 16;7:11581
27181366
Nat Commun. 2015 Jun 17;6:7351
26081979
Breast Cancer Res. 2011 Aug 31;13(4):R84
21884573
Lancet Oncol. 2014 Sep;15(10 ):1100-8
25163906
Cell Stem Cell. 2010 May 7;6(5):421-32
20452317
Curr Opin Cell Biol. 2015 Oct;36:23-31
26186729
Cell. 2016 Mar 24;165(1):45-60
27015306
EMBO Mol Med. 2013 Apr;5(4):488-508
23436775
Annu Rev Cell Dev Biol. 2011;27:291-320
21663443
Nat Commun. 2016 Jun 23;7:11942
27336951
J Natl Cancer Inst. 2014 Jun 28;106(8):null
24974129
J Biol Chem. 2015 Feb 20;290(8):4545-51
25568317
Cancer Discov. 2012 Aug;2(8):706-21
22609699
Oncogene. 2016 Apr 14;35(15):1899-908
26148229
Dev Cell. 2014 May 27;29(4):421-36
24814316
Oncogene. 2014 May 22;33(21):2779-89
23792450
Curr Opin Cell Biol. 2016 Apr;39:93-100
26930633
Cancer Discov. 2016 May;6(5):516-31
26811325
Trends Cell Biol. 2015 Apr;25(4):234-40
25572304
Nat Med. 2011 Mar;17(3):320-9
21383745
Genes Dev. 2009 Feb 15;23 (4):397-418
19240129
Nat Med. 2016 May;22(5):497-505
27089513
Cell. 2006 Aug 11;126(3):489-502
16901783
Cell. 2015 Sep 24;163(1):160-73
26406376
Cell. 2001 Nov 30;107(5):643-54
11733063
Nat Commun. 2016 Aug 04;7:12237
27488962
Cancer Res. 2009 Nov 15;69(22):8620-8
19887601
Nat Rev Cancer. 2010 Jan;10(1):9-22
20029421
Oncotarget. 2015 Jan 20;6(2):715-31
25596732
Nat Med. 2011 Jun 26;17(7):867-74
21706029
Cancer Cell. 2015 Apr 13;27(4):574-88
25873177
Nat Cell Biol. 2013 Apr;15(4):338-44
23548926
Nat Mater. 2014 Jun;13(6):631-7
24793358
Am J Pathol. 2011 Mar;178(3):1221-32
21356373
Mol Cells. 2013 Jul;36(1):1-6
23686429
Nat Cell Biol. 2015 Nov;17 (11):1412-21
26436690
Nature. 2015 Nov 19;527(7578):329-35
26524530
EMBO Rep. 2014 Dec;15(12):1243-53
25381661
Nature. 2015 Oct 1;526(7571):131-5
26416748