EphB3 suppresses non-small-cell lung cancermetastasis via a PP2A/RACK1/Akt signallingcomplex

摘要

Eph receptors are implicated in regulating the malignant progression of cancer. Here we find thatdespite overexpression of EphB3 in human non-small-cell lung cancer, as reported previously, theexpression of its cognate ligands, either ephrin-B1 or ephrin-B2, is significantly downregulated,leading to reduced tyrosine phosphorylation of EphB3. Forced activation of EphB3 kinase inEphB3-overexpressing non-small-cell lung cancer cells inhibits cell migratory capability in vitroas well as metastatic seeding in vivo. Furthermore, we identify a novel EphB3-binding protein,the receptor for activated C-kinase 1, which mediates the assembly of a ternary signal complexcomprising protein phosphatase 2A, Akt and itself in response to EphB3 activation, leading toreduced Akt phosphorylation and subsequent inhibition of cell migration. our study revealsa novel tumour-suppressive signalling pathway associated with kinase-activated EphB3 innon-small-cell lung cancer, and provides a potential therapeutic strategy by activating EphB3signalling, thus inhibiting tumour metastasis.