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