HTLV-1 activates YAP via NF-κB/p65 to promote oncogenesis

Abstract

Significance The Hippo pathway plays critical roles in controlling cell proliferation, and its dysregulation is widely implicated in numerous human cancers. YAP, a Hippo signaling effector, often acts as a nexus and integrator for multiple prominent signaling networks. In this study, we discover NF-κB cross talk with the Hippo pathway and identify p65 as a critical regulator for YAP nuclear retention and transcriptional activity. Furthermore, we find that p65-induced YAP activation is essential for maintaining the proliferation of ATL cells in vitro and in vivo. Our findings unravel the functional interplay between NF-κB and YAP signaling and provide mechanistic insights into the YAP-dependent growth control pathway and tumorigenesis.