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
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.


2020 ◽  
Vol 217 (6) ◽  
Author(s):  
Liwei An ◽  
Pingping Nie ◽  
Min Chen ◽  
Yang Tang ◽  
Hui Zhang ◽  
...  

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.


Gene ◽  
2018 ◽  
Vol 641 ◽  
pp. 240-247 ◽  
Author(s):  
Li Li ◽  
Jianguo Zhao ◽  
Shanshan Huang ◽  
Yi Wang ◽  
Lingling Zhu ◽  
...  

2018 ◽  
Vol 233 (6) ◽  
pp. 4606-4617 ◽  
Author(s):  
Wanlei Yang ◽  
Weiqi Han ◽  
An Qin ◽  
Ziyi Wang ◽  
Jiake Xu ◽  
...  

2020 ◽  
Vol 52 (8) ◽  
pp. 875-882
Author(s):  
Yajie Zhou ◽  
Yanfei Li ◽  
Junwei Shen ◽  
Jue Li ◽  
Xinming Li

Abstract Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor that has received approval from the US Food and Drug Administration for using in patients with advanced breast cancer. However, its potential adverse effects on cardiomyocytes remain unknown. In this study, we used the cell counting kit-8 assay, western blot analysis, flow cytometry, immunostaining, and quantitative polymerase chain reaction to investigate the role of abemaciclib in inducing apoptosis and in inhibiting the viability and proliferation of AC16 human cardiomyocyte cells. The results revealed that abemaciclib induced apoptosis and inhibited cell proliferation by activating the Hippo signaling pathway. This work demonstrates the molecular basis by which abemaciclib induces cardiac side effects, providing a theoretical basis and effective targets for the treatment of cardiac diseases.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2438 ◽  
Author(s):  
Sahar Sarmasti Emami ◽  
Derek Zhang ◽  
Xiaolong Yang

The Hippo pathway is an emerging tumor suppressor signaling pathway involved in a wide range of cellular processes. Dysregulation of different components of the Hippo signaling pathway is associated with a number of diseases including cancer. Therefore, identification of the Hippo pathway regulators and the underlying mechanism of its regulation may be useful to uncover new therapeutics for cancer therapy. The Hippo signaling pathway includes a set of kinases that phosphorylate different proteins in order to phosphorylate and inactivate its main downstream effectors, YAP and TAZ. Thus, modulating phosphorylation and dephosphorylation of the Hippo components by kinases and phosphatases play critical roles in the regulation of the signaling pathway. While information regarding kinase regulation of the Hippo pathway is abundant, the role of phosphatases in regulating this pathway is just beginning to be understood. In this review, we summarize the most recent reports on the interaction of phosphatases and the Hippo pathway in tumorigenesis. We have also introduced challenges in clarifying the role of phosphatases in the Hippo pathway and future direction of crosstalk between phosphatases and the Hippo pathway.


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