THE INTERPLAY BETWEEN RUNX3 AND TEAD-YAP COMPLEX IN GASTRIC CANCER

Abstract

RUNX3 is a well-documented tumour suppressor, whose inactivation, either due to promoter methylation or protein mislocalization, is frequently observed in gastric cancer. TEAD-YAP complex is a transcriptional factor regulating cell proliferation and migration. In normal quiescent adult cells, the activity of TEAD-YAP complex is restricted at a low level by Hippo pathway as well as other mechanisms, while the hyper-activation of TEAD-YAP complex is frequently observed in liver cancer and breast cancer. In this study, we proved that the TEAD-YAP complex also conferred strong oncogenic activities in gastric epithelial cells. The higher expression of TEAD-YAP in tumour tissues significantly correlated with poorer overall survival time in a gastric cancer cohort. Strikingly, RUNX3 physically interacted TEAD (TEA domain family members) proteins through its Runt domain. This interaction markedly reduced the DNA binding ability of TEAD, which attenuated the downstream signalling of TEAD-YAP complex.