VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer

doi:10.1038/ncomms14058

	VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer
	Jiao, Shi 1; Li, Chuanchuan 1; Hao, Qian 1; Miao, Haofei 1; Zhang, Lei1,2 ; Li, Lin2,3 ; Zhou, Zhaocai1,2
	2017-01-04
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	8
发表状态	已发表
DOI	10.1038/ncomms14058
摘要	Concerted co-regulation of multiple signalling pathways is crucial for tissue homoeostasis and tumorigenesis. Here we report that VGLL4, a previously identified YAP antagonist, also functions as a regulator of Wnt/beta-catenin signalling. The expression of VGLL4 is significantly downregulated in clinical colorectal carcinoma (CRC) specimens, positively associated with patient survival rate, and inversely correlated with the expression of Wnt target genes in CRCs. Knockdown of VGLL4 enhances proliferation and tumour formation of CRC cells. A designed peptide mimicking the function of VGLL4 effectively inhibits CRC progression in a de novo mouse model. Mechanistically, TEAD4 associates with TCF4 to form a complex and cobind target genes. VGLL4 targets this TEAD4-TCF4 complex to interfere the functional interplay between TEAD4 and TCF4, suppressing the transactivation of TCF4. Collectively, our study indicates that Wnt/beta-catenin and Hippo-YAP signalling are directly linked at transcription factor-level, and VGLL4 can target a TEAD4-TCF4 complex to co-regulate both pathways.
收录类别	SCI
语种	英语
资助项目	'Strategic Priority Research Program' of the Chinese Academy of Sciences[XDA12020342] ; 'Strategic Priority Research Program' of the Chinese Academy of Sciences[XDB19000000]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000391195700001
出版者	NATURE PUBLISHING GROUP
WOS关键词	ORGAN SIZE CONTROL ; TRANSCRIPTIONAL COACTIVATOR ; CELL-PROLIFERATION ; TISSUE-GROWTH ; YAP ; PATHWAY ; YORKIE ; BETA ; INHIBITION ; REPRESSION
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1553
专题	生命科学与技术学院_特聘教授组_李林组生命科学与技术学院_特聘教授组_张雷组生命科学与技术学院_特聘教授组_周兆才组
通讯作者	Zhou, Zhaocai
作者单位	1.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biol Sci, State Key Lab Cell Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Jiao, Shi,Li, Chuanchuan,Hao, Qian,et al. VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer[J]. NATURE COMMUNICATIONS,2017,8.
APA	Jiao, Shi.,Li, Chuanchuan.,Hao, Qian.,Miao, Haofei.,Zhang, Lei.,...&Zhou, Zhaocai.(2017).VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer.NATURE COMMUNICATIONS,8.
MLA	Jiao, Shi,et al."VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer".NATURE COMMUNICATIONS 8(2017).