Chen Shen, Jezabel Rodriguez-Blanco, Carsten Krieg, Kathryn G Lindsey, Heather J McCrea, Vanesa Martin, Timothy R Gershon, Avencia Sanchez-Mejias, Daniel T Wynn, Marzena Swiderska-Syn, Benjamin R Babcock, Fan Yang, Cara Seward, Sean M Greiner, April D Salvador, Olga Schleuger, Alexander Oles, Júlia Mir-Pedrol
Journal: Science advances 2022;8(29):eabj9138
PMID: 35857834
SRY (sex determining region Y)-box 2 (SOX2)-labeled cells play key roles in chemoresistance and tumor relapse; thus, it is critical to elucidate the mechanisms propagating them. Single-cell transcriptomic analyses of the most common malignant pediatric brain tumor, medulloblastoma (MB), revealed the existence of astrocytic cells expressing sonic hedgehog (SHH) signaling biomarkers. Treatment with vismodegib, an SHH inhibitor that acts on Smoothened (Smo), led to increases in astrocyte-like cells. Using SOX2-enriched MB cultures, we observed that SOX2 cells required SHH signaling to propagate, and unlike in the proliferative tumor bulk, the SHH pathway was activated in these cells downstream of Smo in an MYC-dependent manner. Functionally different GLI inhibitors depleted vismodegib-resistant SOX2 cells from MB tissues, reduced their ability to further engraft in vivo, and increased symptom-free survival. Our results emphasize the promise of therapies targeting GLI to deplete SOX2 cells and provide stable tumor remission.
Full Text Sources:
Medical:
Miscellaneous:
Molecular Biology Databases:
Full Text Sources:
Research Materials:
© Copyright 2026, Nutrition Evidence
We use cookies to improve your experience and analyze site traffic with Google Analytics. By continuing to use our site, you agree to our use of cookies. Learn more.