Aberrant activation and interactions of hedgehog (HH) and PI3K/AKT/mTOR signaling pathways are frequently associated with high-risk medulloblastoma (MB).
These results suggest that LncRNA LOXL1-AS1 promoted the proliferation and metastasis of medulloblastoma by activating the PI3K-AKT pathway, providing evidence that knockdown of LncRNA LOXL1-AS1 might be a potential therapeutic strategy against medulloblastoma.
Therefore our study identifies a compartmentalized PtdIns(3,4,5)P<sub>3</sub>/AKT/GSK3β signaling axis at cilia in SHH-dependent medulloblastoma that is regulated by INPP5E to maintain tumor cell cilia, promote SHH signaling and thereby medulloblastoma progression.
Human neural stem and progenitor cells transformed with c-MYC, dominant-negative p53, constitutively active AKT and hTERT formed tumors in mice that recapitulated Group 3 medulloblastoma in terms of pathology and expression profile.
Increasing PID1 also increased cell death and apoptosis, inhibited proliferation, induced mitochondrial depolaization, and decreased serum-mediated phosphorylation of AKT and ERK in medulloblastoma, ATRT, and/or GBM cell lines, whereas siRNA to PID1 diminished mitochondrial depolarization.
Due to promising results of preclinical studies investigating the PI3K/AKT pathway in grade IV brain tumors like glioblastoma and medulloblastoma, the components of this pathway have emerged as promising therapeutic targets to treat these malignant brain tumors.
To investigate if an activated PI3K/AKT pathway is required for medulloblastoma cell growth, we treated five human medulloblastoma cell lines with increasing concentrations of the PI3K inhibitor LY294002 and analyzed cellular proliferation and apoptosis.
These findings correlate with the fact that phosphorylated forms of the downstream-signaling molecules Erk-1, Erk-2, and Akt/protein kinase B were found in medulloblastoma biopsies but not in control cerebellar tissue.