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https://www.readbyqxmd.com/read/28990064/gaseous-signalling-molecule-so2-via-hippo%C3%A2-mst-pathway-to-improve-myocardial-fibrosis-of-diabetic-rats
#1
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)...
October 4, 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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28919443/fv-clasp-an-artificially-designed-small-antibody-fragment-with-improved-production-compatibility-stability-and-crystallizability
#5
Takao Arimori, Yu Kitago, Masataka Umitsu, Yuki Fujii, Ryoko Asaki, Keiko Tamura-Kawakami, Junichi Takagi
Antibody fragments are frequently used as a "crystallization chaperone" to aid structural analysis of complex macromolecules that are otherwise crystallization resistant, but conventional fragment formats have not been designed for this particular application. By fusing an anti-parallel coiled-coil structure derived from the SARAH domain of human Mst1 kinase to the variable region of an antibody, we succeeded in creating a novel chimeric antibody fragment of ∼37 kDa, termed "Fv-clasp," which exhibits excellent crystallization compatibility while maintaining the binding ability of the original IgG molecule...
September 6, 2017: Structure
https://www.readbyqxmd.com/read/28893403/energy-restriction-affect-liver-development-in-hu-sheep-ram-lambs-through-hippo-signaling-pathway
#6
Ting-Ting Zhang, Guo-Min Zhang, Yu-Hang Jin, Yi-Xuan Guo, Zhen Wang, Yi-Xuan Fan, M A El-Samahy, Feng Wang
This study aimed to evaluate the effects of dietary energy restriction on postnatal liver development in Hu sheep ram lambs. A total of 16 ram lambs were randomly divided into two groups: 100% energy requirements diet and 55% energy requirements diet, which were fed for 75 d. Results showed that the final body and liver weights decreased with energy restriction (p <0.05). Energy restriction caused a significant decrease in the levels of circulating insulin-like growth factor 1 (IGF1) and an increase in growth hormone secretion (p <0...
September 2, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28880957/mapping-the-stk4-hippo-signaling-network-in-prostate-cancer-cell
#7
Damien Ready, Kader Yagiz, Pooneh Amin, Yuksel Yildiz, Vincent Funari, Serdar Bozdag, Bekir Cinar
Dysregulation of MST1/STK4, a key kinase component of the Hippo-YAP pathway, is linked to the etiology of many cancers with poor prognosis. However, how STK4 restricts the emergence of aggressive cancer remains elusive. Here, we investigated the effects of STK4, primarily localized in the cytoplasm, lipid raft, and nucleus, on cell growth and gene expression in aggressive prostate cancer. We demonstrated that lipid raft and nuclear STK4 had superior suppressive effects on cell growth in vitro and in vivo compared with cytoplasmic STK4...
2017: PloS One
https://www.readbyqxmd.com/read/28866620/hepatic-hippo-signaling-inhibits-protumoural-microenvironment-to-suppress-hepatocellular-carcinoma
#8
Wantae Kim, Sanjoy Kumar Khan, Yuchen Liu, Ruoshi Xu, Ogyi Park, Yong He, Boksik Cha, Bin Gao, Yingzi Yang
OBJECTIVE: Hippo signalling is a recently identified major oncosuppressive pathway that plays critical roles in inhibiting hepatocyte proliferation, survival and hepatocellular carcinoma (HCC) formation. Hippo kinase (Mst1 and Mst2) inhibits HCC proliferation by suppressing Yap/Taz transcription activities. As human HCC is mainly driven by chronic liver inflammation, it is not clear whether Hippo signalling inhibits HCC by shaping its inflammatory microenvironment. DESIGN: We have established a genetic HCC model by deleting Mst1 and Mst2 in hepatocytes...
September 2, 2017: Gut
https://www.readbyqxmd.com/read/28856101/draft-genome-sequence-of-an-endophytic-bacterium-paenibacillus-tyrfis-strain-suk123-isolated-from-santiria-apiculata-stem
#9
Emmanuel Haruna, Noraziah M Zin, Jonathan M Adams
Here we report the draft genome sequence of an endophytic Paenibacillus tyrfis strain isolated from the Universiti Kebangsaan Malaysia reserve forest, Malaysia. The genome size was approximately 8.04 Mb, and the assembly consisted of 107 scaffolds with 168 contigs, and had a G + C content of 53%. Phylogenetic analysis of strain SUK123 using the 16S rRNA gene revealed that it belonged to the family Paenibacillaceae with the highest similarity to Paenibacillus elgii SD(T) (99%). Whole genome comparison of SUK123 with related species using average nucleotide identity (ANI) analysis revealed a similarity of 98% to Paenibacillus tyrfis Mst1(T), 94% to Paenibacillus elgii B69(T), 91% to Paenibacillus ehimensis A2(T), 68% to Paenibacillus polymyxa SC2(T) and 69% to Paenibacillus alvei DMS29(T)...
December 2017: Genomics Data
https://www.readbyqxmd.com/read/28835703/neuroprotective-effects-of-cgp3466b-on-apoptosis-are-modulated-by-protein-l-isoaspartate-d-aspartate-o-methyltransferase-mst1-pathways-after-traumatic-brain-injury-in-rats
#10
Feng Liang, Ligen Shi, Jingwei Zheng, Sheng Chen, Yangxin Wang, Jianmin Zhang
Neuronal apoptosis chiefly contributes to the cell loss following traumatic brain injury (TBI). CGP3466B is a compound related to the anti-Parkinsonism drug R-(-)-deprenyl. Previous studies have illuminated anti-apoptosis effects of CGP3466B in different cell lines, but the underlying mechanisms have not been fully elucidated. Mammalian sterile 20 (STE20)-like kinase1 (Mst1) is a core component of the Hippo signaling pathway. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is an enzyme that repairs damaged L-isoaspartyl residues in proteins...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28823082/mir-3910-promotes-the-growth-and-migration-of-cancer-cells-in-the-progression-of-hepatocellular-carcinoma
#11
Lina Cheng, Hongwei Wang, Shuangyin Han
INTRODUCTION: Previous studies have reported that specific depletion of mammalian sterile-like kinase (MST1) in the mouse liver driven Hepatocellular carcinoma (HCC). However, how the expression of MST1 was regulated in the progression of HCC remains largely unknown. MATERIALS AND METHODS: The expression of miR-3910 in the HCC tissues and cell lines were examined using q-PCR. The functions of miR-3910 in HCC were examined using MTT assay, Boyden chamber assay and soft agar assay...
October 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28814946/protein-signatures-of-molecular-pathways-in-non-small-cell-lung-carcinoma-nsclc-comparison-of-glycoproteomics-and-global-proteomics
#12
Shuang Yang, Lijun Chen, Daniel W Chan, Qing Kay Li, Hui Zhang
BACKGROUND: Non-small cell lung carcinoma (NSCLC) remains the leading cause of cancer deaths in the United States. More than half of NSCLC patients have clinical presentations with locally advanced or metastatic disease at the time of diagnosis. The large-scale genomic analysis of NSCLC has demonstrated that molecular alterations are substantially different between adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). However, a comprehensive analysis of proteins and glycoproteins in different subtypes of NSCLC using advanced proteomic approaches has not yet been conducted...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28802229/tgf-%C3%AE-mediated-repression-of-mst1-by-dnmt1-promotes-glioma-malignancy
#13
Zhifei Guo, Guangyuan Li, Erbao Bian, Chun-Chun Ma, Jinghai Wan, Bing Zhao
Human gliomas are related to high rates of morbidity and mortality. TGF-β promotes the growth of glioma cells, and correlate with the degree of malignancy of human gliomas. However, the molecular mechanisms involved in the malignant function of TGF-β are not fully elucidated. Here, we showed that TGF-β induced the downregulation of MST1 expression in U87 and U251 glioma cells. Treatment of glioma cells with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-AzadC) prevented the loss of MST1 expression...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28757479/the-functions-of-the-hippo-signaling-pathway-in-immune-cells
#14
Shu-juan Yu, Jing Geng, Lan-fen Chen
The Hippo signaling pathway, first identified in Drosophila, has emerged as a critical regulator for controlling the size of organs. Activation of the Hippo signaling pathway negatively regulates the Yorkie ortholog YAP in multiple organs, important in the regulation of cell proliferation, differentiation, and apoptosis during development. The Serine/Threonine protein kinases MST1 and MST2, mammalian homologs of the Drosophila Hippo kinase, play central roles in the Hippo signaling pathway in mammals. Recent studies reveal that non-canonical Hippo signaling pathways are also involved in the regulation of various other biological processes, particularly the important roles of MST1 and MST2 kinases in immune cell activation, adhesion, migration, growth, and apoptosis...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28757478/the-roles-and-mechanisms-of-mst1-2-in-the-innate-immune-response
#15
Xin Zhou, Wei-yun Li, Hong-yan Wang
The Hippo signaling pathway regulates cell proliferation, organ size and tissue regeneration through a series of kinase cascades. MST1/2 is the mammalian orthologue of the core kinase Hippo, which is crucial for the activation of downstream signaling. Additionally, MST1/2 has been reported to play important roles in cell differentiation, morphology and cytoskeleton reorganization. Recent evidence suggests that MST1/2 is involved in the regulation of T cell adhesion, migration, homing and Treg cell maturation and functions...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28753558/hgfl-mediated-ron-signaling-supports-breast-cancer-stem-cell-phenotypes-via-activation-of-non-canonical-%C3%AE-catenin-signaling
#16
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...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28752853/regulation-of-hippo-pathway-transcription-factor-tead-by-p38-mapk-induced-cytoplasmic-translocation
#17
Kimberly C Lin, Toshiro Moroishi, Zhipeng Meng, Han-Sol Jeong, Steven W Plouffe, Yoshitaka Sekido, Jiahuai Han, Hyun Woo Park, Kun-Liang Guan
The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer. The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD)...
July 28, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28698384/palmitic-acid-dysregulates-the-hippo-yap-pathway-and-inhibits-angiogenesis-by-inducing-mitochondrial-damage-and-activating-the-cytosolic-dna-sensor-cgas-sting-irf3-signaling-mechanism
#18
Liangshuai Yuan, Yun Mao, Wei Luo, Weiwei Wu, Hao Xu, Xing Li Wang, Ying H Shen
Impaired angiogenesis and wound healing carry significant morbidity and mortality in diabetic patients. Metabolic stress from hyperglycemia and elevated free fatty acids have been shown to inhibit endothelial angiogenesis. However, the underlying mechanisms remain poorly understood. In this study, we show that dysregulation of the Hippo-Yes-associated protein (YAP) pathway, an important signaling mechanism in regulating tissue repair and regeneration, underlies palmitic acid (PA)-induced inhibition of endothelial angiogenesis...
September 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28612556/-effects-of-msp-on-the-proliferation-migration-and-invasion-of-human-non-small-cell-lung-cancer-cells
#19
Xia Liu, Shi-Hang Wei, Xue-Ni Shi, Yi-Nan Zuo, Xue-Ling He, Hai-Lin Yin
OBJECTIVES: To determine the effects of macrophage stimulating protein (Msp) on the proliferation, migration and invasion of human non-small cell lung cancer cells PC14. METHODS: The eukaryotic expression vector for st1was constructed and transfected into Msp(-)and RON(-)human non-small cell lung cancer cells PC14. The expression of st1mRNA in PC14 cells was observed by RT-PCR. The expression levels of Msp protein in PC14, PC14-st1-pEGFP-N1 and PC14-pEGFP-N1 groups as well as the expression of RON in PC14 and SKBR-3 cells were detected by Western blot...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28552397/morin-attenuates-diethylnitrosamine-induced-rat-liver-fibrosis-and-hepatic-stellate-cell-activation-by-co-ordinated-regulation-of-hippo-yap-and-tgf-%C3%AE-1-smad-signaling
#20
NaveenKumar Perumal, MadanKumar Perumal, Devaraj Halagowder, NiranjaliDevaraj Sivasithamparam
Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-β1 (TGF-β1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-β1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/β-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-β1/Smad pathways was not determined...
September 2017: Biochimie
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