High-Throughput Flow Cytometry Screening Reveals a Role for Junctional Adhesion Molecule A as a Cancer Stem Cell Maintenance Factor
oleh: 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
| Format: | Article |
|---|---|
| Diterbitkan: | Elsevier 2014-01-01 |
Deskripsi
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.