Analysis of patient data further identified EPHB2 overexpression in HNSCC tumors to be associated with poor patient prognosis and tumor angiogenesis, especially in the context of overexpression of the exosome secretion regulator cortactin.
The inhibition of receptor phosphorylation was correlated with a decrease in VEGF-triggered phosphorylation of angiogenesis signal molecules AKT and ERK, but not stress-related JNK.
In summary, we demonstrated that EGFRvIII induces Angptl4 expression through the ERK/c-Myc pathway and promotes tumor angiogenesis in malignant gliomas.
Taken together, these data demonstrate that secreted protein alphastatin inhibits VEGF- or bFGF-induced angiogenesis by suppressing JNK and ERK kinases activation pathways in HUVECs, and markedly inhibits tumor angiogenesis in vivo.