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Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  • Masahiro Hitomi
  • Anastasia P Chumakova
  • Daniel J Silver
  • Arnon M Knudsen
  • W Dean Pontius
  • Stephanie Murphy
  • Neha Anand
  • Bjarne W Kristensen
  • Justin D Lathia
Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummere130510
TidsskriftJCI Insight
Vol/bind6
Udgave nummer3
ISSN2379-3708
DOI
StatusUdgivet - 8 feb. 2021

ID: 71934730