BTG2 - BTG2 Is A Medulloblastoma Suppressor

BTG2 Is A Medulloblastoma Suppressor

BTG2 has been shown to inhibit medulloblastoma, the very aggressive tumor of cerebellum, by inhibiting the proliferation and triggering the diffentiation of the precursors of cerebellar granule neurons. This demonstration was obtained by overexpressing BTG2 in a mouse model of medulloblastoma, presenting activation of the Sonic Hedgehog pathway (heterozygous for the gene Patched1). More recently, it has been shown that the ablation of BTG2 greatly enhances the medulloblastoma frequency by inhibiting the migration of cerebellar granule neuron precursors. This impairment of migration of the precursors of cerebellar granule neurons forces them to remain at the surface of the cerebellum, where they continue to proliferate, becoming target of transforming insults. The impairment of migration of the precursors of cerebellar granule neurons (GCPs) depends on the inhibition of expression of the chemokine CXCL3 consequent to ablation of BTG2. In fact, the transcription of CXCL3 is directly regulated by BTG2, and CXCL3 is able to induce cell-autonomously the migration of cerebellar granule precursors. Remarkably, the treatment with CXCL3 reduces the area of medulloblastoma lesions. Thus, CXCL3 is a potential target for medulloblastoma therapy.