title: A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer.
abstract: 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.
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Shi
authors: S
authors: Jiao
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Huizhen
authors: H
authors: Wang
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Zhubing
authors: Z
authors: Shi
authors: Department of Gastroenterology and Internal Medicine, Nanjing Xiaguan Hospital, Nanjing, Jiangsu 210085, China.
authors: Aimei
authors: A
authors: Dong
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Wenjing
authors: W
authors: Zhang
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Xiaomin
authors: X
authors: Song
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Feng
authors: F
authors: He
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Yicui
authors: Y
authors: Wang
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Zhenzhen
authors: Z
authors: Zhang
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Wenjia
authors: W
authors: Wang
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Xin
authors: X
authors: Wang
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Tong
authors: T
authors: Guo
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Peixue
authors: P
authors: Li
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Yun
authors: Y
authors: Zhao
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China. Electronic address: hbji@sibcb.ac.cn.
authors: Hongbin
authors: H
authors: Ji
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China. Electronic address: rayzhang@sibcb.ac.cn.
authors: Lei
authors: L
authors: Zhang
authors: National Center for Protein Science Shanghai, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China. Electronic address: zczhou@sibcb.ac.cn.
authors: Zhaocai
authors: Z
authors: Zhou
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008875:Middle Aged; D018716:Molecular Mimicry; D009124:Muscle Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011487:Protein Conformation; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D000091262:TEA Domain Transcription Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000964:Antimetabolites, Antineoplastic; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D014157:Transcription Factors; C488533:VGLL4 protein, human; C456659:YY1AP1 protein, human; D005472:Fluorouracil