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

被引：671

作者：

Jiao, Shi ^{[1
]}

Wang, Huizhen ^{[1
]}

Shi, Zhubing ^{[1
]}

Dong, Aimei ^{[2
]}

Zhang, Wenjing ^{[1
]}

Song, Xiaomin ^{[1
]}

He, Feng ^{[1
]}

Wang, Yicui ^{[1
]}

Zhang, Zhenzhen ^{[1
]}

Wang, Wenjia ^{[1
]}

Wang, Xin ^{[1
]}

Guo, Tong ^{[1
]}

Li, Peixue ^{[1
]}

Zhao, Yun ^{[1
]}

Ji, Hongbin ^{[1
]}

Zhang, Lei ^{[1
]}

Zhou, Zhaocai ^{[1
]}

机构：

[1] Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, State Key Lab Cell Biol, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[2] Nanjing Xiaguan Hosp, Dept Gastroenterol & Internal Med, Nanjing 210085, Jiangsu, Peoples R China

来源：

CANCER CELL | 2014年 / 25卷 / 02期

基金：

中国国家自然科学基金;

关键词：

HIPPO SIGNALING PATHWAY; YES-ASSOCIATED PROTEIN; CELL CONTACT INHIBITION; TISSUE GROWTH-FACTOR; ORGAN SIZE CONTROL; GENE-EXPRESSION; DROSOPHILA HOMOLOG; TEAD/TEF FAMILY; DOWN-REGULATION; YORKIE;

D O I：

10.1016/j.ccr.2014.01.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：166 / 180

页数：15

共 54 条

[1]

YAP oncogene overexpression supercharges colon cancer proliferation [J].