A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer
A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer
复制标题
模拟 VGLL4 功能的肽作为 YAP 拮抗剂治疗胃癌
DOI：
10.1016/j.ccr.2014.01.010
复制
发表时间：
2014-02-10
期刊：
影响因子：
50.3
通讯作者：
Zhou, Zhaocai
中科院分区：
文献类型：
--
作者：
Jiao, Shi;Wang, Huizhen;Zhou, Zhaocai
Hippo通路通过限制雅普的致癌活性而参与抑制组织过度生长和肿瘤形成。然而，抑制雅普活性的转录调节因子尚未得到很好的研究。在这里，我们揭示了VGLL 4在胃癌抑制中的临床重要性，并发现VGLL 4直接与雅普竞争结合TEAD。重要的是，VGLL 4的串联Tondu结构域对于其对雅普的抑制活性不仅是必需的，而且是足够的。模拟VGLL 4的这种功能的肽在体外和体内有效地抑制肿瘤生长。这些发现表明，通过VGLL 4模拟肽破坏YAP-TEAD相互作用可能是针对YAP驱动的人类癌症的有希望的治疗策略。
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's 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 vitro and in 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.