Abstract:
:Of the erythropoietin-producing human hepatocellular receptors (Ephs), EphB4 has recently emerged as a potential target in several cancers due to its roles in modified cell migration and invasion. As little is known about the roles of EphB4 in glioma, we sought to investigate its function in glioma by in vitro cell migration and invasion assays, immunoblotting and immunostaining. EphB4 was expressed in glioma cell lines and stem-like cell lines. The stimulation of glioma cells with ephrin-B2, the sole ligand of EphB4, conducted EphB4 phosphorylation and suppressed migration and invasion that downregulation of EphB4 using small interfering RNA abrogated. The stimulation also suppressed the phosphorylation of Akt. We confirmed by immunostaining that EphB4-positive cells existing only in the tumor core, whereas ephrin-B2-positive cells widespread in both the tumor core and the invasive area signifying that EphB4-ephrin-B2 reaction occurred only at the tumor core. Taken together, our data suggest that ephrin-B2-dependent EphB4 phosphorylation acts as an anchoring signal to reduce the malignancy by inhibiting Akt phosphorylation in the glioma core, whereas the scarcity of signaling in the tumor periphery promotes invasion into the surrounding brain.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Kawahara Y,Furuta T,Sabit H,Tamai S,Dong Y,Jiapaer S,Zhang J,Zhang G,Oishi M,Miyashita K,Hayashi Y,Nakada Mdoi
10.1016/j.canlet.2019.02.021subject
Has Abstractpub_date
2019-05-01 00:00:00pages
56-65eissn
0304-3835issn
1872-7980pii
S0304-3835(19)30099-0journal_volume
449pub_type
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