YAP1

Pathology

 YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. (#19952108#)

• Medulloblastoma is the most common solid malignancy of childhood, with treatment side effects reducing survivors’ quality of life and lethality being associated with tumor recurrence.
• Activation of the Sonic hedgehog (Shh) signaling pathway is implicated in human medulloblastomas.
• Cerebellar granule neuron precursors (CGNPs) depend on signaling by the morphogen Shh for expansion during development, and have been suggested as a cell of origin for certain medulloblastomas.
• Tere is an up-regulation of the oncogenic transcriptional coactivator yes-associated protein 1 (YAP1), which is negatively regulated by the Hippo pathway, in human medulloblastomas with aberrant Shh signaling.
• Consistent with conserved mechanisms between brain tumorigenesis and development, Shh induces YAP1 expression in CGNPs.
• Shh also promotes YAP1 nuclear localization in CGNPs, and YAP1 can drive CGNP proliferation.
• YAP1 is found in cells of the perivascular niche, where proposed tumor-repopulating cells reside.
• Post-irradiation, YAP1 was found in newly growing tumor cells.
• YAP1 as a new Shh effector that may be targeted by medulloblastoma therapies aimed at eliminating medulloblastoma recurrence.

References

 YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Fernandez-L A, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, Taylor MD, Kenney AM. Genes Dev. 2009 Dec 1;23(23):2729-41. PMID: #19952108# [Free]