scholarly journals MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway

2020 ◽  
Vol 217 (6) ◽  
Author(s):  
Liwei An ◽  
Pingping Nie ◽  
Min Chen ◽  
Yang Tang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Poor Prognosis ◽  
Human Gastric Cancer ◽  
Hippo Signaling ◽  
Wild Type ◽  
Hippo Signaling Pathway ◽  
Phosphorylation Level ◽  
Signaling Axis ◽  
Importin Α

Hyperactivation of YAP has been commonly associated with tumorigenesis, and emerging evidence hints at multilayered Hippo-independent regulations of YAP. In this study, we identified a new MST4–YAP axis, which acts as a noncanonical Hippo signaling pathway that limits stress-induced YAP activation. MST4 kinase directly phosphorylated YAP at Thr83 to block its binding with importin α, therefore leading to YAP cytoplasmic retention and inactivation. Due to a consequential interplay between MST4-mediated YAP phospho-Thr83 signaling and the classical YAP phospho-Ser127 signaling, the phosphorylation level of YAP at Thr83 was correlated to that at Ser127. Mutation of T83E mimicking MST4-mediated alternative signaling restrained the activity of both wild-type YAP and its S127A mutant mimicking loss of classical Hippo signal. Depletion of MST4 in mice promoted gastric tumorigenesis with diminished Thr83 phosphorylation and hyperactivation of YAP. Moreover, loss of MST4–YAP signaling was associated with poor prognosis of human gastric cancer. Collectively, our study uncovered a noncanonical MST4–YAP signaling axis essential for suppressing gastric tumorigenesis.

scholarly journals Effects of the Hippo Signaling Pathway in Human Gastric Cancer

2013 ◽  
Vol 14 (9) ◽  
pp. 5199-5205 ◽  
Author(s):  
Guang-Xi Zhou ◽  
Xiao-Yu Li ◽  
Qi Zhang ◽  
Kun Zhao ◽  
Cui-Ping Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Human Gastric Cancer ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

MiR-93-5p promotes gastric cancer-cell progression via inactivation of the Hippo signaling pathway

Gene ◽  
2018 ◽  
Vol 641 ◽  
pp. 240-247 ◽  
Author(s):  
Li Li ◽  
Jianguo Zhao ◽  
Shanshan Huang ◽  
Yi Wang ◽  
Lingling Zhu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Cell Progression

scholarly journals Potential Role of Hippo-Signaling Pathway in Gastric Cancer

OALib ◽  
2016 ◽  
Vol 03 (03) ◽  
pp. 1-7
Author(s):  
Noman Ali ◽  
Muhammad Asim ◽  
Raheel Asghar ◽  
Awais Amin ◽  
Muhammad Saif Ur Rahman
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Potential Role ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

scholarly journals The Mutation of Ednrb(c.857 T > C) Associated With Atrophied Spleen Phenotype in Mice 

2021 ◽  
Author(s):  
Fei Wu ◽  
Mei Li ◽  
Fu-Wen Wang ◽  
Yuan Gao ◽  
Tariq Munir ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Signal Pathway ◽  
Hippo Signaling ◽  
Wild Type ◽  
Hippo Signaling Pathway ◽  
Chemokine Signaling ◽  
Chemokine Signaling Pathway ◽  
Upregulated Genes ◽  
Small Spleen

Abstract Background:The endothelin signaling pathway plays an important function in the migration, proliferation, and differentiation of neural crest cells. Endothelin receptor B (EDNRB) was reported to have a small spleen phenotype in its deficient mouse model .In our study, we also found that the mutation of EDNRB gene (c. 857 T > c) led to an atrophied spleen phenotype in mice. Different genotypes of EDNRB were significantly correlated with the spleen-kidney ratio, and the spleen phenotypes of Ednrbm1yzcm mice were smaller. The results of the tissue section and H&E staining showed that the spleen microstructure of Ednrbm1yzcm mice was abnormal. In order to explore the molecular mechanism, three groups of Ednrbm1yzcm and wild-type mice were used as control, and standard |log2(FoldChange)|>1 and Padj<0.05 were used to study the influence of EDNRB gene mutation on spleen transcriptional group in mice. GO and KEGG enrichment analysis was conducted to explore the signal pathway related to small spleen phenotype.Results: Through sequencing of mouse spleen transcriptome, 121 differentially expressed genes were selected. Results of the KEGG pathway enrichment analysis showed that in Ednrbm1yzcm mice, upregulated genes were significantly enriched in the Hippo signaling pathway, this pathway inhibits cell growth and modulates organs size and volume; and down-regulation of immune functionally associated pathways such as cytokine receptor interaction and chemokine signaling pathway. In addition, chemokine of Chemokine signaling pathway may also be related to the development of spleen immune tissue structure.Conclusions: In the experiment, we found that mice with mutations in the EDNRB gene have features such as an atrophied spleen and changes in the structure of the spleen. In order to explore the reasons, we performed RNA sequencing on three groups of Edrnrbm1yzcm and wild-type mice, and we found that upregulated genes were significantly enriched in the Hippo signaling pathway. And this signal Pathway is a proven signaling pathway that controls organ size and immune function, so we speculate that the size of the spleen may be related to the Hippo signaling pathway. This study provides a theoretical study of the mechanism of spleen development.

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