Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells.
AC133 Antigen
/ metabolism
Asymmetric Cell Division
Brain Neoplasms
/ drug therapy
Cell Differentiation
Cell Line, Tumor
Cell Self Renewal
Drug Resistance, Neoplasm
ErbB Receptors
/ antagonists & inhibitors
Gene Knockdown Techniques
Glioblastoma
/ drug therapy
Humans
Neoplastic Stem Cells
/ drug effects
Nerve Tissue Proteins
/ antagonists & inhibitors
Receptors, Nerve Growth Factor
/ antagonists & inhibitors
Brain cancer
Cancer
Cell Biology
Stem cells
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
08 02 2021
08 02 2021
Historique:
received:
22
05
2019
accepted:
16
12
2020
pubmed:
23
12
2020
medline:
29
5
2021
entrez:
22
12
2020
Statut:
epublish
Résumé
Asymmetric cell division (ACD) enables the maintenance of a stem cell population while simultaneously generating differentiated progeny. Cancer stem cells (CSCs) undergo multiple modes of cell division during tumor expansion and in response to therapy, yet the functional consequences of these division modes remain to be determined. Using a fluorescent reporter for cell surface receptor distribution during mitosis, we found that ACD generated a daughter cell with enhanced therapeutic resistance and increased coenrichment of EGFR and neurotrophin receptor (p75NTR) from a glioblastoma CSC. Stimulation of both receptors antagonized differentiation induction and promoted self-renewal capacity. p75NTR knockdown enhanced the therapeutic efficacy of EGFR inhibition, indicating that coinheritance of p75NTR and EGFR promotes resistance to EGFR inhibition through a redundant mechanism. These data demonstrate that ACD produces progeny with coenriched growth factor receptors, which contributes to the generation of a more therapeutically resistant CSC population.
Identifiants
pubmed: 33351787
pii: 130510
doi: 10.1172/jci.insight.130510
pmc: PMC7934841
doi:
pii:
Substances chimiques
AC133 Antigen
0
NGFR protein, human
0
Nerve Tissue Proteins
0
PROM1 protein, human
0
Receptors, Nerve Growth Factor
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R03 CA215939
Pays : United States
Références
Nature. 2006 Dec 7;444(7120):756-60
pubmed: 17051156
J Immunol Methods. 2009 Aug 15;347(1-2):70-8
pubmed: 19567251
Curr Opin Cell Biol. 2020 Dec;67:9-16
pubmed: 32768924
Cancer Cell. 2011 Sep 13;20(3):328-40
pubmed: 21907924
Cancer Res. 2014 Aug 15;74(16):4536-48
pubmed: 24947043
Cell Stem Cell. 2018 Apr 5;22(4):514-528.e5
pubmed: 29625067
Science. 2014 Jun 20;344(6190):1396-401
pubmed: 24925914
Cell Stem Cell. 2018 Feb 1;22(2):221-234.e8
pubmed: 29395056
Cancer Res. 2018 Aug 1;78(15):4360-4369
pubmed: 29844123
Biophys J. 2001 May;80(5):2120-32
pubmed: 11325715
Nat Rev Drug Discov. 2013 Jul;12(7):507-25
pubmed: 23977697
Ann Oncol. 2017 Jul 1;28(7):1448-1456
pubmed: 28407030
Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):1985-96
pubmed: 25053711
PLoS One. 2016 Mar 08;11(3):e0151274
pubmed: 26953813
J Pathol. 2018 Mar;244(3):260-264
pubmed: 29282720
Cancer Res. 2016 Apr 15;76(8):2443-52
pubmed: 26893479
Handb Exp Pharmacol. 2014;220:103-19
pubmed: 24668471
Nat Med. 2017 Oct 6;23(10):1124-1134
pubmed: 28985214
J Cell Biol. 2018 Nov 5;217(11):3785-3795
pubmed: 30232100
Cancer Cell. 2015 Oct 12;28(4):441-455
pubmed: 26461092
Nat Commun. 2018 Jun 21;9(1):2424
pubmed: 29930325
Cancer Res. 1997 Mar 1;57(5):978-87
pubmed: 9041204
Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2264-71
pubmed: 16609043
Elife. 2016 Apr 14;5:
pubmed: 27077950
Cytometry A. 2019 Mar;95(3):290-301
pubmed: 30729665
Cell Death Dis. 2011 Sep 01;2:e200
pubmed: 21881602
Clin Pharmacol Ther. 2011 Apr;89(4):491-502
pubmed: 21368752
Curr Biol. 2019 Oct 21;29(20):3466-3477.e4
pubmed: 31607534
Neuro Oncol. 2018 May 18;20(6):743-752
pubmed: 29040782
Stem Cell Reports. 2015 Jul 14;5(1):1-9
pubmed: 26095605
Nat Genet. 2014 Mar;46(3):245-52
pubmed: 24487275
Oncotarget. 2018 Apr 24;9(31):22095-22112
pubmed: 29774125
PLoS Biol. 2007 Aug;5(8):e212
pubmed: 17696644
Cancer Treat Rev. 2006 Apr;32(2):74-89
pubmed: 16488082
Neuro Oncol. 2016 Jul;18(7):914-8
pubmed: 26755074
Cell. 2009 Sep 18;138(6):1083-95
pubmed: 19766563
Neuro Oncol. 2014 Jul;16(7):984-90
pubmed: 24637230
Cell. 2008 Feb 22;132(4):583-97
pubmed: 18295577
J Neurosci. 2006 May 17;26(20):5288-300
pubmed: 16707781
Cancer Res. 2006 Oct 1;66(19):9339-44
pubmed: 16990346
Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9
pubmed: 11413487
Nat Commun. 2018 Aug 21;9(1):2862
pubmed: 30131568
Curr Treat Options Oncol. 2008 Feb;9(1):23-31
pubmed: 18247132
Stem Cells. 2012 Apr;30(4):591-8
pubmed: 22331764
J Clin Invest. 2017 Feb 1;127(2):415-426
pubmed: 28145904
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16766-71
pubmed: 20826440
Stem Cells Int. 2016;2016:1740936
pubmed: 27418931
Cancer Res. 2016 Jun 1;76(11):3411-21
pubmed: 27197180
J Clin Oncol. 2009 Mar 10;27(8):1268-74
pubmed: 19204207
Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):625-630
pubmed: 30587593
Cell Stem Cell. 2016 Feb 4;18(2):189-202
pubmed: 26849305
Nat Cell Biol. 2000 Sep;2(9):582-92
pubmed: 10980698
Nat Phys. 2019 Jun 24;15(10):1075-1085
pubmed: 31579399
Int J Radiat Oncol Biol Phys. 1997 Nov 1;39(4):789-95
pubmed: 9369124