EB1 acts as an oncogene via activating beta-catenin/TCF pathway to promote cellular growth and inhibit apoptosis.

Previously we showed that end-binding protein 1 (EB1) may promote cellular growth by activating beta-catenin/T-cell factor (TCF) pathway. To further investigate the role of EB1 in regulating cellular growth, we established an EB1-inducible expression system in which the protein level of EB1 was significantly upregulated upon doxycycline induction. We found that EB1 promoted cellular growth and resulted in a significant increase in colony formation. In addition, EB1 could induce tumor formation in nude mice, activate beta-catenin-dependent gene expression and upregulate the transcriptional activity of c-myc. We also showed that EB1 in this manner inhibited apoptosis of 293-T-REx cells upon cisplatin and upregulated expression of Bcl-2, whereas DeltaN TCF4, an inhibitor of beta-catenin/TCF pathway, could completely or partially abolish the effects of EB1 on the promotion of cell growth and the inhibition of apoptosis activity. Moreover, knockdown of c-myc by RNAi could abrogate upregulation of EB1-dependent induction of Bcl-2 expression. Overall, EB1 acts as a potential oncogene via activating beta-catenin/TCF pathway to promote cellular growth and inhibit apoptosis.