Misshapen Disruption Cooperates with to Drive Tumorigenesis.

Although family genes play essential roles in tumorigenesis, effective treatments targeting -related tumors are lacking, partly because of an incomplete understanding of the complex signaling crosstalk within -related tumors. Here, we performed a large-scale genetic screen in eye imaginal discs and identified () as a tumor suppressor that synergizes with oncogenic () to induce c-Jun N-terminal kinase (JNK) activation and Hippo inactivation, then subsequently leads to tumor overgrowth and invasion. Moreover, ectopic Msn expression activates Hippo signaling pathway and suppresses Hippo signaling disruption-induced overgrowth. Importantly, we further found that Msn acts downstream of protocadherin Fat (Ft) to regulate Hippo signaling. Finally, we identified as a Yki/Sd target gene that regulates Hippo pathway in a negative feedback manner. Together, our findings identified Msn as a tumor suppressor and provide a novel insight into -related tumorigenesis that may be relevant to human cancer biology.