A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer

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• 作者：Shi Jiao ; Huizhen Wang ; Zhubing Shi ; Aimei Dong ; Wenjing Zhang ; Xiaomin Song ; Feng He ; Yicui Wang ; Zhenzhen Zhang ; Wenjia Wang ; Xin Wang ; Tong Guo ; Peixue Li ; Yun Zhao ; Hongbin Ji ; Lei Zhang ; Zhaocai Zhou
• 刊名：Cancer Cell
• 出版年：10 February, 2014
• 年：2014
• 卷：25
• 期：2
• 页码：166-180
• 全文大小：4389 K

文摘

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Summary

The Hippo pathway has been implicated in suppressing tissue overgrowth and tumor formation by restricting the oncogenic activity of YAP. However, transcriptional regulators that inhibit YAP activity have not been well studied. Here, we uncover clinical importance for VGLL4 in gastric cancer suppression and find that VGLL4 directly competes with YAP for binding TEADs. Importantly, VGLL4鈥檚 tandem Tondu domains are not only essential but also sufficient for its inhibitory activity toward YAP. A peptide mimicking this function of VGLL4 potently suppressed tumor growth in聽vitro and in聽vivo. These findings suggest that disruption of YAP-TEADs interaction by a VGLL4-mimicking peptide may be a promising therapeutic strategy against YAP-driven human cancers.