Display options
Cite
Keulers TG, Libregts SF, Beaumont JEJ, et al. Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1. J Extracell Vesicles. 2021;10(14):e12166doi: 10.1002/jev2.12166.
Keulers, T. G., Libregts, S. F., Beaumont, J. E. J., Savelkouls, K. G., Bussink, J., Duimel, H., Dubois, L., Zonneveld, M. I., López-Iglesias, C., Bezstarosti, K., Demmers, J. A., Vooijs, M., Wauben, M., & Rouschop, K. M. A. (2021). Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1. Journal of extracellular vesicles, 10(14), e12166. https://doi.org/10.1002/jev2.12166
Keulers, Tom G, et al. "Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1." Journal of extracellular vesicles vol. 10,14 (2021): e12166. doi: https://doi.org/10.1002/jev2.12166
Keulers TG, Libregts SF, Beaumont JEJ, Savelkouls KG, Bussink J, Duimel H, Dubois L, Zonneveld MI, López-Iglesias C, Bezstarosti K, Demmers JA, Vooijs M, Wauben M, Rouschop KMA. Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1. J Extracell Vesicles. 2021 Dec;10(14):e12166. doi: 10.1002/jev2.12166. PMID: 34859607; PMCID: PMC8640512.
Copy Download .nbib Format: NLM
Share it on

J Extracell Vesicles. 2021 Dec;10(14):e12166. doi: 10.1002/jev2.12166.

Secretion of pro-angiogenic extracellular vesicles during hypoxia is dependent on the autophagy-related protein GABARAPL1.

Journal of extracellular vesicles

Tom G Keulers, Sten F Libregts, Joel E J Beaumont, Kim G Savelkouls, Johan Bussink, Hans Duimel, Ludwig Dubois, Marijke I Zonneveld, Carmen López-Iglesias, Karel Bezstarosti, Jeroen A Demmers, Marc Vooijs, Marca Wauben, Kasper M A Rouschop

Affiliations

  1. Department of Radiation Oncology Radiation Oncology (Maastro) / GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre +, Maastricht, Netherlands.
  2. Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
  3. Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands.
  4. Microscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute, FHML Division of Nanoscopy, University of Maastricht, Maastricht, Netherlands.
  5. The M-Lab, Department of Precision Medicine, GROW - School of Oncology, Maastricht University, Maastricht, Netherlands.
  6. Proteomics Center, Erasmus University Medical Center, Rotterdam, Netherlands.

PMID: 34859607 PMCID: PMC8640512 DOI: 10.1002/jev2.12166

Abstract

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

© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

Keywords: GABARAPL1; autophagy; exosomes; extracellular vesicles; hypoxia

References

  1. Cell. 1995 Nov 3;83(3):423-32 - PubMed
  2. Mol Cell Biol. 2012 May;32(9):1733-44 - PubMed
  3. Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7312-7 - PubMed
  4. Cytometry A. 2016 Feb;89(2):135-47 - PubMed
  5. FASEB J. 2016 Dec;30(12):3961-3978 - PubMed
  6. Cancer Lett. 2020 Jun 1;479:23-30 - PubMed
  7. Traffic. 2003 Nov;4(11):754-71 - PubMed
  8. Cell. 1988 Jan 15;52(1):73-83 - PubMed
  9. Biochem Biophys Res Commun. 2020 Sep 10;530(1):292-300 - PubMed
  10. Cancer Med. 2018 Mar;7(3):820-830 - PubMed
  11. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):285-9 - PubMed
  12. Exp Hematol. 2019 Aug;76:60-66.e2 - PubMed
  13. Cancer Res. 1996 Oct 1;56(19):4509-15 - PubMed
  14. Science. 2008 Feb 29;319(5867):1244-7 - PubMed
  15. Cell. 1996 Aug 9;86(3):353-64 - PubMed
  16. Mol Cell Proteomics. 2009 Dec;8(12):2770-7 - PubMed
  17. Nat Cell Biol. 2002 May;4(5):394-8 - PubMed
  18. Nat Rev Cancer. 2002 Jan;2(1):38-47 - PubMed
  19. Nat Commun. 2021 Jun 2;12(1):3292 - PubMed
  20. Nat Methods. 2017 Feb 28;14(3):228-232 - PubMed
  21. Nat Rev Mol Cell Biol. 2010 May;11(5):329-41 - PubMed
  22. Mol Cancer Res. 2018 Nov;16(11):1798-1808 - PubMed
  23. Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22 - PubMed
  24. Radiother Oncol. 2015 Sep;116(3):417-22 - PubMed
  25. J Cell Sci. 2018 Aug 3;131(15): - PubMed
  26. Autophagy. 2016;12(1):1-222 - PubMed
  27. J Clin Invest. 2010 Jan;120(1):127-41 - PubMed
  28. Mol Cancer. 2014 Apr 26;13:88 - PubMed
  29. Cell Death Discov. 2021 May 6;7(1):94 - PubMed
  30. J Biol Chem. 2013 Nov 29;288(48):34343-51 - PubMed
  31. Cells. 2020 Jun 16;9(6): - PubMed
  32. Cell. 2005 Sep 9;122(5):735-49 - PubMed
  33. Front Immunol. 2014 Sep 16;5:442 - PubMed
  34. J Cell Sci. 2006 Feb 15;119(Pt 4):605-14 - PubMed
  35. EMBO J. 2010 Jun 2;29(11):1792-802 - PubMed
  36. J Cell Biol. 2016 Dec 19;215(6):857-874 - PubMed
  37. Adv Exp Med Biol. 2018;1074:335-343 - PubMed
  38. Nat Protoc. 2016 Dec;11(12):2301-2319 - PubMed
  39. Cancers (Basel). 2019 Jan 29;11(2): - PubMed
  40. Dev Cell. 2017 Dec 18;43(6):716-730.e7 - PubMed
  41. Mol Cancer. 2019 Jan 31;18(1):18 - PubMed
  42. Commun Biol. 2019 Oct 18;2:386 - PubMed
  43. Semin Cancer Biol. 2014 Oct;28:24-30 - PubMed
  44. Nat Cell Biol. 2020 Feb;22(2):187-199 - PubMed
  45. J Extracell Vesicles. 2018 Nov 23;7(1):1535750 - PubMed
  46. J Biol Chem. 2006 Feb 10;281(6):3017-24 - PubMed
  47. EMBO J. 2011 Aug 31;30(17):3481-500 - PubMed
  48. Nat Cell Biol. 2014 May;16(5):415-24 - PubMed
  49. J Intern Med. 2015 Sep;278(3):251-63 - PubMed
  50. Nat Rev Cancer. 2008 Nov;8(11):851-64 - PubMed
  51. Histochem Cell Biol. 2010 Jan;133(1):41-55 - PubMed
  52. Oncotarget. 2015 Sep 15;6(27):24404-23 - PubMed
  53. Clin Cancer Res. 2017 Aug 15;23(16):4843-4854 - PubMed
  54. Exp Cell Res. 2009 May 15;315(9):1584-92 - PubMed
  55. Cell. 2015 May 21;161(5):1046-1057 - PubMed
  56. Nat Protoc. 2006;1(6):2813-9 - PubMed
  57. Cell. 1992 Sep 4;70(5):715-28 - PubMed
  58. Nat Cell Biol. 2015 Mar;17(3):300-10 - PubMed
  59. Front Oncol. 2016 Nov 25;6:251 - PubMed
  60. Int J Clin Oncol. 2021 Oct;26(10):1831-1839 - PubMed
  61. Radiother Oncol. 2005 Oct;77(1):18-24 - PubMed
  62. BMC Cancer. 2019 Jan 7;19(1):14 - PubMed
  63. Nat Protoc. 2012 Jun 14;7(7):1311-26 - PubMed

Publication Types

Grant support