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https://www.readbyqxmd.com/read/29222344/trip6-inhibits-hippo-signaling-in-response-to-tension-at-adherens-junctions
#1
Shubham Dutta, Sebastian Mana-Capelli, Murugan Paramasivam, Ishani Dasgupta, Heather Cirka, Kris Billiar, Dannel McCollum
The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here, we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension...
December 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29219182/the-emerging-role-of-hippo-signaling-pathway-in-regulating-osteoclast-formation
#2
REVIEW
Wanlei Yang, Weiqi Han, An Qin, Ziyi Wang, Jiake Xu, Yu Qian
A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29214772/pseudolaric-acid-b-inhibits-proliferation-invasion-and-epithelial-to-mesenchymal-transition-in-human-pancreatic-cancer-cell
#3
Xiaoyu Li, Xianzhi Zhao, Wen Song, Zibin Tian, Lin Yang, Qinghui Niu, Qi Zhang, Man Xie, Bin Zhou, Yonghong Xu, Jun Wu, Cuiping Zhang
PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules...
January 2018: Yonsei Medical Journal
https://www.readbyqxmd.com/read/29209784/acaxl2-and-acmst1-regulate-arthrospore-development-and-stress-resistance-in-the-cephalosporin-c-producer-acremonium-chrysogenum
#4
Janina Kluge, Ulrich Kück
The filamentous fungus Acremonium chrysogenum is the primordial producer of the β-lactam antibiotic cephalosporin C. This antibiotic is of major biotechnological and medical relevance because of its antibacterial activity against Gram-positive and Gram-negative bacteria. Antibiotic production during the lag phase of fermentation is often accompanied by a typical morphological feature of A. chrysogenum, the fragmentation of the mycelium into arthrospores. Here, we sought to identify factors that regulate the hyphal septation process and present the first comparative functional characterization of the type I integral plasma membrane protein Axl2 (axial budding pattern protein 2), a central component of the bud site selection system (BSSS) and Mst1 (mammalian Sterile20-like kinase), a septation initiation network (SIN)-associated germinal center kinase (GCK)...
December 5, 2017: Current Genetics
https://www.readbyqxmd.com/read/29195393/1-%C3%AE-s-broadband-frequency-sweeping-reflectometry-for-plasma-density-and-fluctuation-profile-measurements
#5
F Clairet, C Bottereau, A Medvedeva, D Molina, G D Conway, A Silva, U Stroth
Frequency swept reflectometry has reached the symbolic value of 1 μs sweeping time; this performance has been made possible, thanks to an improved control of the ramp voltage driving the frequency source. In parallel, the memory depth of the acquisition system has been upgraded and can provide up to 200 000 signals during a plasma discharge. Additional improvements regarding the trigger delay determination of the acquisition and the voltage ramp linearity required by this ultra-fast technique have been set...
November 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/29155025/understanding-the-role-of-mammalian-sterile-20-like-kinase-1-mst1-in-cardiovascular-disorders
#6
REVIEW
Yang Yang, Haichang Wang, Zhiqiang Ma, Wei Hu, Dongdong Sun
Hippo signaling is a conserved pathway and plays important role in controlling cell proliferation and differentiation. As critical components of the Hippo pathway in mammals, mammalian sterile 20-like kinase 1 (MST1) participate in cell apoptosis and cell proliferation. Yes-associated protein (YAP) acts as a downstream transcriptional co-activator of MST1. MST1 is present in heart tissue and helps determine the fate of cardiomyocytes by regulating the balance between autophagy and apoptosis. Recent studies showed MST1 signaling is an essential participant in many cardiovascular disorders, including aortic dissection, aortic aneurysm, atherosclerosis, myocardial ischemic injury, and cardiomyopathy...
November 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29127009/nicorandil-alleviates-myocardial-injury-and-post-infarction-cardiac-remodeling-by-inhibiting-mst1
#7
Shanjie Wang, Yanhong Fan, Xinyu Feng, Chuang Sun, Zhaofeng Shi, Tian Li, Jianjun Lv, Zhi Yang, Zhijing Zhao, Dongdong Sun
BACKGROUND: Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI. METHODS: A cardiac MI injury model was constructed by ligating the left anterior descending (LAD) coronary artery...
November 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29112934/long-non-coding-rna-gas5-antagonizes-the-chemoresistance-of-pancreatic-cancer-cells-through-down-regulation-of-mir-181c-5p
#8
Zhi-Qiang Gao, Jun-Feng Wang, De-Hua Chen, Xue-Song Ma, Wu Yang, Tang Zhe, Xiao-Wei Dang
OBJECTIVE: To explore the core mechanism of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the regulation of multidrug resistance of pancreatic cancer cells. METHODS: mRNA levels of GAS5, miR-181c-5p and Hippo pathway related genes were detected by quantitative real-time PCR (qRT-PCR). Protein levels of MDR-1, MST1, YAP and TAZ were measured by western blot. Cell viability was detected by MTT assay. The combination between GAS5 and miR-181c-5p was confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assay...
November 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29108261/the-coiled-coil-domain-of-oncogene-rassf-7-inhibits-hippo-signaling-and-promotes-non-small-cell-lung-cancer
#9
Xiaoying Zheng, Qianze Dong, Xiupeng Zhang, Qiang Han, Xu Han, Yong Han, Jingjing Wu, Xuezhu Rong, Enhua Wang
Lung cancer is the leading cause of cancer-related deaths worldwide, and despite recent improvements in treatment patient prognosis remains dismal. In this study, we examined the role of N-terminal Ras-association domain family 7 (RASSF7) in human non-small cell lung cancer (NSCLC). We found that RASSF7 was overexpressed NSCLC tissues, which correlated with advanced TNM stage, positive lymph node metastasis, and poor prognosis. This RASSF7 overexpression promoted lung cancer cell proliferation, migration, and invasion...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108216/-research-advances-in-the-role-of-the-hippo-signaling-pathway-in-pathogenesis-of-liver-cancer
#10
L Yuan, Z W Li
The Hippo signaling pathway consists of four core components in mammals, i.e., Mst1/2, WW45, Mob1, and LATS1/2, which can inhibit the transcriptional coactivator YAP from entering the nucleus, maintain the balance between cell proliferation and apoptosis, control organ size, and maintain homeostasis. If the core components of the Hippo signaling pathway are inactivated due to gene mutation or epigenetic alterations, YAP is overexpressed and activated in the nucleus, which then induces excessive cell proliferation and inhibits cell apoptosis...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29098035/mammalian-sterile-20-like-kinase-1-expression-and-its-prognostic-significance-in-patients-with-breast-cancer
#11
Xiao-Yan Lin, Feng-Feng Cai, Ming-Hong Wang, Xin Pan, Fang Wang, Lu Cai, Rong-Rong Cui, Su Chen, Ewelina Biskup
Mammalian sterile 20-like kinase 1 (Mst1) is a major inhibitor of cell proliferation, and is involved in apoptosis, oncogenesis and organ growth via its ubiquitously encoded serine threonine kinase. Previous studies have demonstrated that Mst1 has a tumor suppressor function in human breast cancer. Mst1 deletion or mutation is associated with tumorigenesis, whereas Mst1 overexpression leads to tumor cell apoptosis and decreases proliferation of tumor cells. Our previous study reported the tumor suppressive function of Mst1, and debated Mst1 as a prognostic factor in human breast cancer...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29079854/identification-of-mst1-as-a-potential-early-detection-biomarker-for-colorectal-cancer-through-a-proteomic-approach
#12
Jiekai Yu, Xiaohui Zhai, Xiaofen Li, Chenhan Zhong, Cheng Guo, Fuquan Yang, Ying Yuan, Shu Zheng
Colorectal cancer (CRC) is a common malignant neoplasm worldwide. It is important to identify new biomarkers for the early detection of CRC. In this study, magnetic beads and the Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) platform were used to analyse CRC and healthy control (HC) serum samples. The CRC diagnosis pattern was established to have a specificity of 94.7% and sensitivity of 92.3% in a blind test. The candidate biomarker serine/threonine kinase 4 (STK4, also known as MST1) was identified by Tandem mass spectrometry (MS/MS) and verified with western blotting and enzyme-linked immunosorbent assay (ELISA)...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29068691/myocardial-injury-is-distinguished-from-stable-angina-by-a-set-of-candidate-plasma-biomarkers-identified-using-itraq-mrm-based-approach
#13
Esther Sok Hwee Cheow, Woo Chin Cheng, Terence Yap, Bamaprasad Dutta, Chuen Neng Lee, Dominique P V de Kleijn, Vitaly Sorokin, Siu Kwan Sze
The lack of precise biomarkers that identify patients at risk for myocardial injury and stable angina delays administration of optimal therapy. Hence, the search for noninvasive biomarkers that could accurately stratify patients with impending heart attack, from patients with stable coronary artery disease (CAD), is urgently needed in the clinic. Herein, we performed comparative quantitative proteomics on whole plasma sampled from patients with stable angina (NMI), acute myocardial infarction (MI), and healthy control subjects (Ctrl)...
November 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29063978/mst1-regulates-colorectal-cancer-stress-response-via-inhibiting-bnip3-related-mitophagy-by-activation-of-jnk-p53-pathway
#14
Qi Li, Feng Qi, Xiangchao Meng, Chenpei Zhu, Yingtang Gao
The Hippo-Mst1 pathway is associated with tumor development and progression. However, little evidence is available for its role in colorectal cancer (CRC) stress response via mitochondrial homeostasis. In this study, we conducted gain-of function assay about Mst1 in CRC via adenovirus transfection. Then, cellular viability and apoptosis were measured via MTT, TUNEL assay, and typan blue staining. Mitochondrial function was detected via JC1 staining, mPTP opening assay, and immunofluorescence of cyt-c. Mitophagy was observed via western blots and immunofluorescence...
October 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29063833/sav1-promotes-hippo-kinase-activation-through-antagonizing-the-pp2a-phosphatase-stripak
#15
Sung Jun Bae, Lisheng Ni, Adam Osinski, Diana R Tomchick, Chad A Brautigam, Xuelian Luo
The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAK(SLMAP) as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains...
October 24, 2017: ELife
https://www.readbyqxmd.com/read/29054447/deletion-ofmst1-attenuates-neuronal-loss-andimproves-neurological-impairment-inarat-model-oftraumatic-brain-injury
#16
Di Li, Haibo Ni, Qin Rui, Rong Gao, Gang Chen
Neuronal cell death following traumatic brain injury (TBI) is a considerable contributor to neurological deficits. In our work, we explored the functions of Mammalian STE20-like kinase-1 (Mst1), a apoptosis-promoting kinase and aslo a pivotal bridgebuilder of apoptotic signaling, in the etiopathogenesis of an experimental rat model of TBI. We found that the phosphorylation level of Mst1 in injured area was significantly increased after TBI. Furthermore, we discovered that inhibition of Mst1 phosphorylation can effectively reduce neuronal cell death by inhibiting the activation of caspase 3 and suppressing the damage of DNA during TBI...
October 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28990064/gaseous-signalling-molecule-so2-via-hippo%C3%A2-mst-pathway-to-improve-myocardial-fibrosis-of-diabetic-rats
#17
Maojun Liu, Shengquan Liu, Wenting Tan, Fen Tang, Junrong Long, Zining Li, Biao Liang, Chun Chu, Jun Yang
Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)‑generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo‑MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague‑Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L‑Aspartic acid β‑hydroxamate (HDX) group (HDX group)...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28947795/stable-mob1-interaction-with-hippo-mst-is-not-essential-for-development-and-tissue-growth-control
#18
Yavuz Kulaberoglu, Kui Lin, Maxine Holder, Zhongchao Gai, Marta Gomez, Belul Assefa Shifa, Merdiye Mavis, Lily Hoa, Ahmad A D Sharif, Celia Lujan, Ewan St John Smith, Ivana Bjedov, Nicolas Tapon, Geng Wu, Alexander Hergovich
The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction...
September 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28938607/hgfl-mediated-ron-signaling-supports-breast-cancer-stem-cell-phenotypes-via-activation-of-non-canonical-%C3%AE-catenin-signaling
#19
Sasha J Ruiz-Torres, Nancy M Benight, Rebekah A Karns, Elyse E Lower, Jun-Lin Guan, Susan E Waltz
Breast cancer stem cells (BCSCs), which drive tumor progression, recurrence, and metastasis, are considered a major challenge for breast cancer treatments, thus the discovery of novel pathways regulating BCSC maintenance remains essential to develop new strategies to effectively target this population and combat disease mortality. The HGFL-RON signaling is overexpressed in human breast cancers and is associated with increased breast cancer progression, metastasis, and poor prognosis. Here, we report that overexpression of RON/MST1R and HGFL/MST1 in cell lines and primary tumors increases BCSC self-renewal, numbers, and tumorigenic potential after syngeneic transplantation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938537/mir-590-3p-promotes-proliferation-and-metastasis-of-colorectal-cancer-via-hippo-pathway
#20
Zhen-Qiang Sun, Ke Shi, Quan-Bo Zhou, Xiang-Yue Zeng, Jinbo Liu, Shuai-Xi Yang, Qi-San Wang, Zhen Li, Gui-Xian Wang, Jun-Min Song, Wei-Tang Yuan, Hai-Jiang Wang
Studies reported that miR-590-3p was involved in human cancer progression. However, its roles of oncogene or anti-oncogene in malignancies still remain elusive. This study was aimed to investigate the effect of miR-590-3p on the cell proliferation and metastasis via Hippo pathway in colorectal cancer (CRC). In our study, miR-590-3p was demonstrated highly expressed in CRC tissues, compared with adjacent normal tissues (P<0.05). In addition, miR-590-3p was positively associated with TNM stage and distant metastasis...
August 29, 2017: Oncotarget
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