UM-6 induces autophagy and apoptosis via the Hippo-YAP signaling pathway in cervical cancer

Melittin's non-specific cytotoxicity and hemolytic activity restrict its clinical use, but polypeptide modification is thoμght to be highly selective and well-tolerated. Here, we synthesized a novel antineoplastic peptide UM-6 based on melittin and explored the mechanism related to its anti-proliferation and metastasis on cervical cancer (CC). In the present study, we demonstrated that UM-6 inhibits viability of CC cell lines Caski and Hela in vitro by inducing apoptosis and autophagy with low toxicity to normal epithelial cells. UM-6 also triggers the Hippo signaling pathway, promoting cytoplasmic retention and phosphorylation-dependent degradation of YAP, as well as inhibiting YAP-TEAD binding and reducing transcriptional activity, suppressing downstream target gene expression. Injection of UM-6 in mice can significantly inhibit the growth of xenograft tumors, and greatly reduce the number, volume, and burden of abdominal tumors in the metastasis models without significant toxicity. These current results suggest that UM-6 has the potential to serve as a new anticancer drug candidate.