VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex

Zhang, Wenjing; Gao, Yijun; Li, Peixue; Shi, Zhubing; Guo, Tong; Li, Fēi; Han, Xiuxin; Feng, Yan; Zheng, Chao; Wang, Zuoyun; Li, Fuming; Chen, Haiquan; Zhou, Zhaocai; Zhang, Lei; Ji, Hongbin

doi:10.1038/cr.2014.10

Cited by 241 publications

(242 citation statements)

References 49 publications

Supporting

Mentioning

226

Contrasting

Order By: Relevance

“…Through a TEAD4-responsive luciferase report, we found that overexpression of Yap significantly enhanced the activity of luciferase reporter (Fig. 3I), as described elsewhere (41). However, ectopic expression of RARg led to a dramatic decrease of Yap-induced luciferase activity (Fig.…”

Section: Rarg Inhibits Yap-tead Transcriptional Activity and Yap Targmentioning

confidence: 78%

See 1 more Smart Citation

RARγ Downregulation Contributes to Colorectal Tumorigenesis and Metastasis by Derepressing the Hippo–Yap Pathway

Guo

Gan

et al. 2016

Cancer Research

View full text Add to dashboard Cite

The Hippo-Yap pathway conveys oncogenic signals, but its regulation during cancer development is not well understood. Here, we identify the nuclear receptor RARg as a regulator of the Hippo-Yap pathway in colorectal tumorigenesis and metastasis. RARg is downregulated in human colorectal cancer tissues, where its expression correlates inversely with tumor size, TNM stage, and distant metastasis. Functional studies established that silencing of RARg drove colorectal cancer cell growth, invasion, and metastatic properties both in vitro and in vivo. Mechanistically, RARg controlled Hippo-Yap signaling to inhibit colorectal cancer development, acting to promote phosphorylation and binding of Lats1 to its transcriptional coactivator Yap and thereby inactivating Yap target gene expression. In clinical specimens, RARg expression correlated with overall survival outcomes and expression of critical Hippo-Yap pathway effector molecules in colorectal cancer patients. Collectively, our results defined RARg as tumor suppressor in colorectal cancer that acts by restricting oncogenic signaling by the Hippo-Yap pathway, with potential implications for new approaches to colorectal cancer therapy.Cancer Res; 76(13); 3813-25. Ó2016 AACR.

show abstract

Section: Rarg Inhibits Yap-tead Transcriptional Activity and Yap Targmentioning

confidence: 78%

“…Yap facilitates regulation of downstream target gene expression by directly binding to the transcription factor TEADs (40,41). Through a TEAD4-responsive luciferase report, we found that overexpression of Yap significantly enhanced the activity of luciferase reporter (Fig.…”

Section: Rarg Inhibits Yap-tead Transcriptional Activity and Yap Targmentioning

confidence: 89%

RARγ Downregulation Contributes to Colorectal Tumorigenesis and Metastasis by Derepressing the Hippo–Yap Pathway

Guo

Gan

et al. 2016

Cancer Research

View full text Add to dashboard Cite

show abstract

“…Suppression of ⌬Np63-Two recent studies suggest that TEAD or its Drosophila homolog Scallop can suppress cellular gene transcription through interaction with transcription cofactor VGLL4 or Tgi, respectively (39,40). However, VGLL4 knockdown in MCF10A cells could not block TAZ-induced suppression of ⌬Np63 (Fig.…”

Section: Modulation Of Deacetylation Is Critical For Taz-tead-inducedmentioning

confidence: 94%

Hippo Component TAZ Functions as a Co-repressor and Negatively Regulates ΔNp63 Transcription through TEA Domain (TEAD) Transcription Factor

Valencia-Sama¹,

Zhao²,

Lai

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…VGLL4 acts as a tumor suppressor in both lung and gastric cancers by repressing YAP-TEAD activity. In addition, a peptide mimicking VGLL4 function acts as a YAP antagonist and shows prominent anti-cancer activity in gastric cancer models [127,128].…”

Section: Teads Are Major Transcription Factor Partners Of Yapmentioning

confidence: 99%

The regulation and function of YAP transcription co-activator

Zhu

Zhao

2015

ABBS

110

View full text Add to dashboard Cite

The Hippo pathway was initially identified in Drosophila by genetic mosaic screens for tumor suppressor genes. Researches indicated that the Hippo pathway is a key regulator of organ size and is conserved during evolution. Furthermore, studies of mouse models and clinical samples demonstrated the importance of Hippo pathway dysregulation in human cancer development. In addition, the Hippo pathway contributes to progenitor cell and stem cell self-renewal and is thus involved in tissue regeneration. In the Hippo pathway, MST1/2 kinases together with the adaptor protein SAV phosphorylate LATS1/2 kinases. Interaction with an adaptor protein MOB is also important for LATS1/2 activation. Activated LATS1/2 in turn phosphorylate and inhibit Yes-associated protein (YAP). YAP is a key downstream effector of the Hippo pathway, and is a transcriptional co-activator that mainly interacts with TEAD family transcription factors to promote gene expression. Alteration of gene expression by YAP leads to cell proliferation, apoptosis evasion, and also stem cell amplification. In this review, we mainly focus on YAP, discussing its regulation and mechanisms of action in the context of organ size control, tissue regeneration and tumorigenesis.

show abstract

VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex

Cited by 241 publications

References 49 publications

RARγ Downregulation Contributes to Colorectal Tumorigenesis and Metastasis by Derepressing the Hippo–Yap Pathway

RARγ Downregulation Contributes to Colorectal Tumorigenesis and Metastasis by Derepressing the Hippo–Yap Pathway

Hippo Component TAZ Functions as a Co-repressor and Negatively Regulates ΔNp63 Transcription through TEA Domain (TEAD) Transcription Factor

The regulation and function of YAP transcription co-activator

Contact Info

Product

Resources

About