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Publication : Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion.

First Author  Liu Y Year  2017
Journal  Cancer Res Volume  77
Issue  23 Pages  6692-6703
PubMed ID  28986380 Mgi Jnum  J:252299
Mgi Id  MGI:6103754 Doi  10.1158/0008-5472.CAN-17-1463
Citation  Liu Y, et al. (2017) Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion. Cancer Res 77(23):6692-6703
abstractText  Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. Although astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here, we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secrete the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drives expression of Nestin in MB cells through a smoothened-dependent, but Gli1-independent mechanism. Ablation of TAA dramatically suppresses Nestin expression and blocks tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression. Cancer Res; 77(23); 6692-703. (c)2017 AACR.
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