Discovery of tertiary amide derivatives incorporating benzothiazole moiety as anti-gastric cancer agents in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway

2020 ◽  
Vol 203 ◽  
pp. 112618 ◽  
Author(s):  
Jian Song ◽  
Qiu-Lei Gao ◽  
Bo-Wen Wu ◽  
Ting Zhu ◽  
Xin-Xin Cui ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Tubulin Polymerization ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Tertiary Amide ◽  
Amide Derivatives

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

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.

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.

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 The long noncoding RNA AATBC promotes breast cancer migration and invasion by interacting with YBX1 and activating the YAP1/Hippo signaling pathway

2021 ◽  
Author(s):  
Maonan Wang ◽  
Manli Dai ◽  
Dan Wang ◽  
Ting Tang ◽  
Fang Xiong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Differentially Expressed ◽  
Migration And Invasion ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

Abstract BackgroundLong noncoding RNAs (lncRNAs) play an important role in the regulation of gene expression and are involved in several pathological responses. However, many important lncRNAs in breast cancer have not been identified and their expression levels and functions in breast cancer remain unknown.MethodsWe used the microarray data to identify differentially expressed lncRNAs between breast cancer and adjacent breast epithelial tissues. In vitro and in vivo assays were used to explore the biological effects of the differentially expressed lncRNA Apoptosis-Associated Transcript in Bladder Cancer (AATBC) in breast cancer cells. The mass spectrometry and RNA pulldown were used to screen AATBC interacting proteins. Using the Kaplan-Meier method, survival analysis was performed.ResultsThe expression of AATBC was significantly high in breast cancer samples, and this high AATBC level was tightly correlated with poor prognosis in breast cancer patients. In vitro and in vivo experiments indicated that AATBC promoted breast cancer cells migration and invasion. AATBC specifically interacted with Y-box binding protein 1 (YBX1), which activated the YAP1/Hippo signaling pathway by binding to macrophage stimulating 1 (MST1) and promoting the nuclear translocation of Yes associated protein 1 (YAP1), allowing its function as a nuclear transcriptional regulator. ConclusionsAATBC is highly expressed in breast cancer and contributes to patients’ progression, indicating that it could serve as a novel prognostic marker for the disease. Mechanistically, AATBC affects migration and invasion of breast cancer cells through an AATBC-YBX1-MST1 axis, resulting in activating the YAP1/Hippo signaling pathway. This is also an important supplement to the composition of the YAP1/Hippo signaling pathway. The model of “AATBC-YAP1” may bring a new dawn to the treatment of breast cancer.

scholarly journals Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue

2020 ◽  
Vol 26 (5) ◽  
pp. 301-311 ◽  
Author(s):  
Susanne Elisabeth Pors ◽  
Lilja Harðardóttir ◽  
Hanna Ørnes Olesen ◽  
Malene Lundgaard Riis ◽  
Lea Bejstrup Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Ovarian Tissue ◽  
Histological Evaluation ◽  
Hippo Signaling ◽  
Preantral Follicles ◽  
Hippo Signaling Pathway ◽  
In Vitro Activation ◽  
Sphingosine 1 Phosphate

Abstract In vitro activation of resting ovarian follicles, with the use of mechanical stress and/or pharmacological compounds, is an emerging and novel approach for infertility treatment. The aim of this study was to assess the sphingolipid, sphingosine-1-phosphate (S1P), as a potential in vitro activation agent in murine and human ovarian tissues and isolated follicles. Juvenile murine ovaries and donated human ovarian tissues, from 10 women undergoing ovarian tissue cryopreservation for fertility preservation, were incubated with or without 12 μM S1P for 3 h for quantitative PCR analysis, and 12 h for xenotransplantation or culture studies. Gene expression analyses were performed for genes downstream of the Hippo signaling pathway. Murine ovaries and isolated murine and human preantral follicles showed significantly increased mRNA expression levels of Ccn2/CCN2 following S1P treatment compared to controls. This increase was shown to be specific for the Hippo signaling pathway and for the S1P2 receptor, as co-treatment with Hippo-inhibitor, verteporfin and S1PR2 antagonist, JTE-013, reduced the S1P-induced Ccn2 gene expression in murine ovaries. Histological evaluation of human cortical tissues (5 × 5 × 1 mm; n = 30; three pieces per patient) xenografted for 6 weeks and juvenile murine ovaries cultured for 4 days (n = 9) or allografted for 2 weeks (n = 48) showed no differences in the distribution of resting or growing follicles in S1P-treated ovarian tissues compared to controls. Collectively, S1P increased Ccn2/CCN2 gene expression in isolated preantral follicles and ovarian tissue from mice and human, but it did not promote follicle activation or growth in vivo. Thus, S1P does not appear to be a potent in vitro activation agent under these experimental conditions.

scholarly journals Hippo Signaling Pathway Reveals a Spatio-Temporal Correlation with the Size of Primordial Follicle Pool in Mice

2015 ◽  
Vol 35 (3) ◽  
pp. 957-968 ◽  
Author(s):  
Cheng Xiang ◽  
Jia Li ◽  
Liaoliao Hu ◽  
Jian Huang ◽  
Tao Luo ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Hippo Pathway ◽  
Temporal Correlation ◽  
Primordial Follicle ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Primordial Follicle Activation ◽  
Spatio Temporal

Background: The Hippo signaling pathway, a highly conserved cell signaling system, exists in most multicellular organisms and regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Hippo signaling are expressed in mammalian ovaries, but the exact functions of this pathway in primordial follicle development remains unclear. Methods: To analyze the spatio-temporal correlation between the core component of Hippo pathway and the size of primordial follicle pool, Western blot, Real-time PCR and immunohistochemistry were used, and the expression and localization of MST1, LATS2 and YAP1 mRNA and protein were examined in 3 d, 1 m, 5 m, 16 m postnatal mice ovary and the culture model of mice primordial follicle in vitro. Results: Both the protein and mRNA expression of the MST1 and LATS2 were decreased significantly as mouse age increased (p < 0.05), however, the mRNA expression of them increased significantly in 16 m compared with 5 m as well as the protein expression of LATS2.The expression of YAP showed the opposite trend, and the significant protein expression of pYAP was increased before 1 m, after which no significant change was observed. Moreover, the ratio of pYAP/YAP decreased significantly. Culturing ovaries for 8 d in vitro resulted in the activation of primordial follicles in 3 d postnatal mice ovaries, and these developed into primary follicles with the expression of PCNA increasing significantly (p < 0.05). The mRNA and protein expression of MST and LATS decreased significantly (p < 0.05), and the expression of YAP increased significantly (p < 0.05, p < 0.01), whereas the ratio of pYAP/YAP decreased significantly (p < 0.05). Conclusion: The above results reveal that the expression of the core components of Hippo pathway changed during mouse follicular development, especially before and after primordial follicle activation in vitro. The primordial follicle activation may be related to the significant decrease of the ratio of pYAP1/YAP1. In conclusion, Hippo signaling pathway expressed in mice ovaries and have spatio-temporal correlation with the size of primordial follicle pool.

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
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