PMC:3583298 / 29977-31212 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/3583298","sourcedb":"PMC","sourceid":"3583298","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3583298","text":"YAP expression is particularly high in the peri-vascular niche (PVN) of medulloblastomas, where the tumor-repopulating cells reside. We have previously shown that 48 hours after radiation, the YAP positive population starts to expand (Fernandez et al 2009). Hambardzumyan et al. (Hambardzumyan et al 2008) elegantly demonstrated that the PI3K-Akt pathway regulates survival of these tumor-repopulating cells residing in the PVN. These results point to the importance of YAP regulating survival and proliferation post-radiation, allowing the cells to skip the cell cycle checkpoints and expand despite the un-repaired damage in their DNA, contributing ultimately to genomic instability. Further studies will address whether YAP-induced genomic instability is solely a consequence of the Akt-mediated cell cycle checkpoint suppression, or whether Akt lying downstream of YAP-induced IGF2 could also inhibit the DNA repair machinery, as previous studies have suggested (Plo et al 2008) (Figure 7). Our results suggest that targeting Akt downstream of YAP would be useful for medulloblastoma therapy in order to reduce the dose of radiation needed and to prevent tumor recurrence, by radiosensitizing PVN-residing tumor-repopulating cells.","tracks":[{"project":"2_test","denotations":[{"id":"21874045-19952108-79138730","span":{"begin":251,"end":255},"obj":"19952108"},{"id":"21874045-19952108-79138730","span":{"begin":251,"end":255},"obj":"19952108"},{"id":"21874045-18281460-79138731","span":{"begin":300,"end":304},"obj":"18281460"},{"id":"21874045-18281460-79138731","span":{"begin":300,"end":304},"obj":"18281460"},{"id":"21874045-19010915-79138732","span":{"begin":977,"end":981},"obj":"19010915"},{"id":"21874045-19010915-79138732","span":{"begin":977,"end":981},"obj":"19010915"}],"attributes":[{"subj":"21874045-19952108-79138730","pred":"source","obj":"2_test"},{"subj":"21874045-19952108-79138730","pred":"source","obj":"2_test"},{"subj":"21874045-18281460-79138731","pred":"source","obj":"2_test"},{"subj":"21874045-18281460-79138731","pred":"source","obj":"2_test"},{"subj":"21874045-19010915-79138732","pred":"source","obj":"2_test"},{"subj":"21874045-19010915-79138732","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#939cec","default":true}]}]}}