Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1.
GABARAPL1
autophagy
exosomes
extracellular vesicles
hypoxia
Journal
Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
21
10
2021
received:
16
10
2020
accepted:
02
11
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
16
3
2022
Statut:
ppublish
Résumé
Tumour hypoxia is a hallmark of solid tumours and contributes to tumour progression, metastasis development and therapy resistance. In response to hypoxia, tumour cells secrete pro-angiogenic factors to induce blood vessel formation and restore oxygen supply to hypoxic regions. Extracellular vesicles (EVs) are emerging as mediators of intercellular communication in the tumour microenvironment. Here we demonstrate that increased expression of the LC3/GABARAP protein family member GABARAPL1, is required for endosomal maturation, sorting of cargo to endosomes and the secretion of EVs. Silencing GABARAPL1 results in a block in the early endosomal pathway and impaired secretion of EVs with pro-angiogenic properties. Tumour xenografts of doxycycline inducible GABARAPL1 knockdown cells display impaired vascularisation that results in decreased tumour growth, elevated tumour necrosis and increased therapy efficacy. Moreover, our data show that GABARAPL1 is expressed on the EV surface and targeting GABARAPL1
Identifiants
pubmed: 34859607
doi: 10.1002/jev2.12166
pmc: PMC8640512
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Autophagy-Related Proteins
0
GABARAPL1 protein, human
0
Microtubule-Associated Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12166Informations de copyright
© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
Références
Cell. 1995 Nov 3;83(3):423-32
pubmed: 8521472
Mol Cell Biol. 2012 May;32(9):1733-44
pubmed: 22354992
Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7312-7
pubmed: 23589885
Cytometry A. 2016 Feb;89(2):135-47
pubmed: 25688721
FASEB J. 2016 Dec;30(12):3961-3978
pubmed: 27601442
Cancer Lett. 2020 Jun 1;479:23-30
pubmed: 32201202
Traffic. 2003 Nov;4(11):754-71
pubmed: 14617358
Cell. 1988 Jan 15;52(1):73-83
pubmed: 3345561
Biochem Biophys Res Commun. 2020 Sep 10;530(1):292-300
pubmed: 32828302
Cancer Med. 2018 Mar;7(3):820-830
pubmed: 29383859
Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):285-9
pubmed: 9226314
Exp Hematol. 2019 Aug;76:60-66.e2
pubmed: 31369790
Cancer Res. 1996 Oct 1;56(19):4509-15
pubmed: 8813149
Science. 2008 Feb 29;319(5867):1244-7
pubmed: 18309083
Cell. 1996 Aug 9;86(3):353-64
pubmed: 8756718
Mol Cell Proteomics. 2009 Dec;8(12):2770-7
pubmed: 19767571
Nat Cell Biol. 2002 May;4(5):394-8
pubmed: 11988743
Nat Rev Cancer. 2002 Jan;2(1):38-47
pubmed: 11902584
Nat Commun. 2021 Jun 2;12(1):3292
pubmed: 34078910
Nat Methods. 2017 Feb 28;14(3):228-232
pubmed: 28245209
Nat Rev Mol Cell Biol. 2010 May;11(5):329-41
pubmed: 20379207
Mol Cancer Res. 2018 Nov;16(11):1798-1808
pubmed: 30042174
Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
pubmed: 18228490
Radiother Oncol. 2015 Sep;116(3):417-22
pubmed: 26164772
J Cell Sci. 2018 Aug 3;131(15):
pubmed: 30076239
Autophagy. 2016;12(1):1-222
pubmed: 26799652
J Clin Invest. 2010 Jan;120(1):127-41
pubmed: 20038797
Mol Cancer. 2014 Apr 26;13:88
pubmed: 24766647
Cell Death Discov. 2021 May 6;7(1):94
pubmed: 33953165
J Biol Chem. 2013 Nov 29;288(48):34343-51
pubmed: 24133215
Cells. 2020 Jun 16;9(6):
pubmed: 32560054
Cell. 2005 Sep 9;122(5):735-49
pubmed: 16143105
Front Immunol. 2014 Sep 16;5:442
pubmed: 25278937
J Cell Sci. 2006 Feb 15;119(Pt 4):605-14
pubmed: 16467569
EMBO J. 2010 Jun 2;29(11):1792-802
pubmed: 20418806
J Cell Biol. 2016 Dec 19;215(6):857-874
pubmed: 27864321
Adv Exp Med Biol. 2018;1074:335-343
pubmed: 29721961
Nat Protoc. 2016 Dec;11(12):2301-2319
pubmed: 27809316
Cancers (Basel). 2019 Jan 29;11(2):
pubmed: 30699970
Dev Cell. 2017 Dec 18;43(6):716-730.e7
pubmed: 29257951
Mol Cancer. 2019 Jan 31;18(1):18
pubmed: 30704479
Commun Biol. 2019 Oct 18;2:386
pubmed: 31646189
Semin Cancer Biol. 2014 Oct;28:24-30
pubmed: 24602822
Nat Cell Biol. 2020 Feb;22(2):187-199
pubmed: 31932738
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
J Biol Chem. 2006 Feb 10;281(6):3017-24
pubmed: 16303767
EMBO J. 2011 Aug 31;30(17):3481-500
pubmed: 21878991
Nat Cell Biol. 2014 May;16(5):415-24
pubmed: 24747438
J Intern Med. 2015 Sep;278(3):251-63
pubmed: 26153525
Nat Rev Cancer. 2008 Nov;8(11):851-64
pubmed: 18846101
Histochem Cell Biol. 2010 Jan;133(1):41-55
pubmed: 19830447
Oncotarget. 2015 Sep 15;6(27):24404-23
pubmed: 26213336
Clin Cancer Res. 2017 Aug 15;23(16):4843-4854
pubmed: 28400428
Exp Cell Res. 2009 May 15;315(9):1584-92
pubmed: 18930046
Cell. 2015 May 21;161(5):1046-1057
pubmed: 26000481
Nat Protoc. 2006;1(6):2813-9
pubmed: 17406539
Cell. 1992 Sep 4;70(5):715-28
pubmed: 1516130
Nat Cell Biol. 2015 Mar;17(3):300-10
pubmed: 25686249
Front Oncol. 2016 Nov 25;6:251
pubmed: 27933272
Int J Clin Oncol. 2021 Oct;26(10):1831-1839
pubmed: 34173120
Radiother Oncol. 2005 Oct;77(1):18-24
pubmed: 16098619
BMC Cancer. 2019 Jan 7;19(1):14
pubmed: 30612555
Nat Protoc. 2012 Jun 14;7(7):1311-26
pubmed: 22722367