We previously reported an angiogenic and
tumor-suppressor-like function of programmed cell death 10 (PDCD10) in
glioblastoma (GBM). However, the underlying mechanism remains to be elucidated. We hypothesized that loss of PDCD10 activates GBM cells and
tumor progression via EphB4. To this end, PDCD10 was knocked down in U87 and T98g by lentiviral mediated
shRNA transduction (shPDCD10). GBM cell phenotype in vitro and
tumor growth in a mouse xenograft model were investigated in presence or absence of the treatment with a specific EphB4
kinase inhibitor
NVP-BHG712 (NVP). We demonstrated that knockdown of PDCD10 in GBM cells significantly upregulated the
mRNA and
protein expression of EphB4 accompanied by the activation of Erk1/2. EphB4
kinase activity, reflected by phospho-EphB4, significantly increased in shPDCD10 GBM cells, and in
tumors derived from shPDCD10 GBM xenografts, which was abolished by the treatment with NVP. Furthermore, NVP treatment significantly suppressed PDCD10-knockdown mediated aggressive GBM cell phenotype in vitro and extensive
tumor cell proliferation, the
tumor neo-angiogenesis, and a quick progression of
tumor formation in vivo. In summary, loss of PDCD10 activates GBM cells and promotes
tumor growth via triggering EphB4. Targeting EphB4 might be an effective strategy particularly for the personalized
therapy in GBM patients with PDCD10-deficiency.