Figure 5.

Interplay mechanism between NTN4 and ITGB4 during glioma progression. At the initial stage of glioma progression, NTN4 concentration stays relatively high in extracellular environment. High concentrations of NTN4 have an ability to reduce cell proliferation through UNC5B. During progression, glioma cells reduce NTN4 expression to prevent the negative effects on glioma cell growth induced by NTN4. In parallel, ITGB4 expression increases. In this way, excessive ITGB4 makes glioblastoma cells hyperresponsive to low concentrations of NTN4 for keeping AKT/mTOR phosphorylation and glioma cell proliferation.