VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer
Jiao, Shi1; Li, Chuanchuan1; Hao, Qian1; Miao, Haofei1; Zhang, Lei1,2; Li, Lin2,3; Zhou, Zhaocai1,2
2017-01-04
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Volume8
Status已发表
DOI10.1038/ncomms14058
AbstractConcerted 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.
Indexed BySCI
Language英语
Funding Project'Strategic Priority Research Program' of the Chinese Academy of Sciences[XDA12020342] ; 'Strategic Priority Research Program' of the Chinese Academy of Sciences[XDB19000000]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000391195700001
PublisherNATURE PUBLISHING GROUP
WOS KeywordORGAN SIZE CONTROL ; TRANSCRIPTIONAL COACTIVATOR ; CELL-PROLIFERATION ; TISSUE-GROWTH ; YAP ; PATHWAY ; YORKIE ; BETA ; INHIBITION ; REPRESSION
Original Document TypeArticle
Citation statistics
Cited Times:69[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1553
Collection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
Corresponding AuthorZhou, Zhaocai
Affiliation1.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
Corresponding Author AffilicationSchool of Life Science and Technology
Recommended Citation
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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