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Publication : A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.

First Author  Amodeo V Year  2017
Journal  Cell Rep Volume  20
Issue  2 Pages  411-426
PubMed ID  28700942 Mgi Jnum  J:254517
Mgi Id  MGI:6104010 Doi  10.1016/j.celrep.2017.06.047
Citation  Amodeo V, et al. (2017) A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS. Cell Rep 20(2):411-426
abstractText  Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells.
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