scholarly journals STK3/4 Expression Is Regulated in Uterine Endometrial Cells during the Estrous Cycle

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1643 ◽  
Author(s):  
Sohyeon Moon ◽  
Ok-Hee Lee ◽  
Sujin Lee ◽  
Jihyun Lee ◽  
Haeun Park ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Estrous Cycle ◽  
Uterine Epithelium ◽  
Hippo Signaling ◽  
Endometrial Cells ◽  
Hippo Signaling Pathway ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Ovariectomized Mice ◽  
Estrus Stage

The uterus is dynamically regulated in response to various signaling triggered by hormones during the estrous cycle. The Hippo signaling pathway is known as an important signaling for regulating cellular processes during development by balancing between cell growth and apoptosis. Serine/threonine protein kinase 3/4 (STK3/4) is a key component of the Hippo signaling network. However, the regulation of STK3/4-Hippo signaling in the uterus is little known. In this study, we investigated the regulation and expression of STK3/4 in the uterine endometrium during the estrous cycle. STK3/4 expression was dynamically regulated in the uterus during the estrous cycle. STK3/4 protein expression was gradually increased from the diestrus stage and reached the highest in the estrus stage. STK3/4 was exclusively localized in the luminal and glandular epithelial cells of the uterus, and phosphorylated STK3/4 was also increased at the estrus stage. Moreover, the increase of STK3/4 expression in uteri was induced by administration of estradiol, but not by progesterone injection in ovariectomized mice. Pretreatment with an estrogen receptor antagonist ICI 182,780 reduced estrogen-induced STK3/4 expression and its phosphorylation. The estrogen-induced STK3/4 expression was related to the increase in phosphorylation of downstream targets including LATS1/2 and YAP. These findings suggest that STK3/4-Hippo signaling acts a novel signaling pathway in the uterine epithelium and STK3/4-Hippo is one of key molecules for connecting between the estrogen downstream signaling pathway and the Hippo signaling pathway leading to regulate dynamic uterine epithelium during the estrous cycle.

scholarly journals Interaction of the Hippo Pathway and Phosphatases in Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2438 ◽  
Author(s):  
Sahar Sarmasti Emami ◽  
Derek Zhang ◽  
Xiaolong Yang
Keyword(s):  
Signaling Pathway ◽  
Hippo Pathway ◽  
Underlying Mechanism ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Cellular Processes ◽  
Wide Range ◽  
Future Direction ◽  
The Hippo Pathway

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.

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 Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

2021 ◽  
Vol 22 (2) ◽  
pp. 931
Author(s):  
Jihyun Lee ◽  
Yujin Jung ◽  
Seo won Jeong ◽  
Ga Hee Jeong ◽  
Gue Tae Moon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Normal Skin ◽  
Skin Lesions ◽  
Hippo Signaling ◽  
Vascular Endothelial ◽  
Expression Levels ◽  
Hippo Signaling Pathway ◽  
Endothelial Growth Factor

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.

Roles of Hippo signaling pathway in size control of organ regeneration

2015 ◽  
Vol 57 (4) ◽  
pp. 341-351 ◽  
Author(s):  
Shinichi Hayashi ◽  
Hitoshi Yokoyama ◽  
Koji Tamura
Keyword(s):  
Signaling Pathway ◽  
Size Control ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Organ Regeneration

scholarly journals Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer

Cell Reports ◽  
2018 ◽  
Vol 25 (5) ◽  
pp. 1304-1317.e5 ◽  
Author(s):  
Yumeng Wang ◽  
Xiaoyan Xu ◽  
Dejan Maglic ◽  
Michael T. Dill ◽  
Kamalika Mojumdar ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Characterization ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

Energy restriction affect liver development in Hu sheep ram lambs through Hippo signaling pathway

2017 ◽  
Vol 49 (5) ◽  
pp. 603-611 ◽  
Author(s):  
Ting-Ting Zhang ◽  
Guo-Min Zhang ◽  
Yu-Hang Jin ◽  
Yi-Xuan Guo ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Energy Restriction ◽  
Liver Development ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Ram Lambs ◽  
Hu Sheep

scholarly journals YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia

2021 ◽  
Vol 8 ◽  
Author(s):  
Chao Zheng ◽  
Jiaqian Luo ◽  
Yifan Yang ◽  
Rui Dong ◽  
Fa-Xing Yu ◽  
...  
Keyword(s):  
Bile Duct ◽  
Liver Fibrosis ◽  
Mouse Model ◽  
Biliary Atresia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Hippo Signaling ◽  
Mice Model ◽  
Hippo Signaling Pathway ◽  
Ductal Cells

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.

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