VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer
2017-01-04
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
卷号8
发表状态已发表
DOI10.1038/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).
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