High-throughput flow cytometry screening reveals a role for junctional adhesion molecule a as a cancer stem cell maintenance factor.

Published

Journal Article

Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytometry screen on patient-derived glioblastoma (GBM) cells and identified junctional adhesion molecule A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function, and JAM-A expression was reduced in normal brain versus GBM. Targeting JAM-A compromised the self-renewal of CSCs. JAM-A expression negatively correlated to GBM patient prognosis. Our results demonstrate that GBM-targeting strategies can be identified through screening adhesion receptors and JAM-A represents a mechanism for niche-driven CSC maintenance.

Full Text

Duke Authors

Cited Authors

  • Lathia, JD; Li, M; Sinyuk, M; Alvarado, AG; Flavahan, WA; Stoltz, K; Rosager, AM; Hale, J; Hitomi, M; Gallagher, J; Wu, Q; Martin, J; Vidal, JG; Nakano, I; Dahlrot, RH; Hansen, S; McLendon, RE; Sloan, AE; Bao, S; Hjelmeland, AB; Carson, CT; Naik, UP; Kristensen, B; Rich, JN

Published Date

  • January 16, 2014

Published In

Volume / Issue

  • 6 / 1

Start / End Page

  • 117 - 129

PubMed ID

  • 24373972

Pubmed Central ID

  • 24373972

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2013.11.043

Language

  • eng

Conference Location

  • United States