학술논문
High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor
Document Type
article
Author
Justin D. Lathia; Meizhang Li; Maksim Sinyuk; Alvaro G. Alvarado; William A. Flavahan; Kevin Stoltz; Ann Mari Rosager; James Hale; Masahiro Hitomi; Joseph Gallagher; Qiulian Wu; Jody Martin; Jason G. Vidal; Ichiro Nakano; Rikke H. Dahlrot; Steinbjørn Hansen; Roger E. McLendon; Andrew E. Sloan; Shideng Bao; Anita B. Hjelmeland; Christian T. Carson; Ulhas P. Naik; Bjarne Kristensen; Jeremy N. Rich
Source
Cell Reports, Vol 6, Iss 1, Pp 117-129 (2014)
Subject
Language
English
ISSN
2211-1247
Abstract
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.