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https://www.readbyqxmd.com/read/28550303/anti-proliferative-effects-of-nucleotides-on-gastric-cancer-via-a-novel-p2y6-soce-ca-2-%C3%AE-catenin-pathway
#1
Hanxing Wan, Rui Xie, Jiangyu Xu, Jialin He, Bo Tang, Qingqing Liu, Sumin Wang, Yanjun Guo, Xin Yang, Tobias Xiao Dong, John M Carethers, Shiming Yang, Hui Dong
Although purinegic signaling is important in regulating gastric physiological functions, it is currently unknown for its role in gastric cancer (GC). We demonstrate for the first time that the expression of P2Y6 receptors was markedly down-regulated in human GC cells and primary GC tissues compared to normal tissues, while the expression of P2Y2 and P2Y4 receptors was up-regulated in GC cells. Moreover, the expression levels of P2Y6 receptors in GC tissues were correlated to tumor size, differentiation, metastasis to lymph nodes, and the survival rate of the patients with GC...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550085/knockdown-of-sodium-calcium-exchanger-1-induces-epithelial-to-mesenchymal-transition-in-kidney-epithelial-cells
#2
Sona Lakshme Balasubramaniam, Anilkumar Gopalakrishnapillai, Nicholas J Petrelli, Sonali P Barwe
Mesenchymal to epithelial transition (MET) and epithelial to mesenchymal transition (EMT) are important processes in kidney development. Failure to undergo MET during development leads to the initiation of Wilms tumor (WT) whereas EMT contributes to the development of renal cell carcinomas (RCC). The role of calcium regulators in governing these processes is becoming evident. We demonstrated earlier that Na+/Ca2+ exchanger 1 (NCX1), a major calcium exporter in renal epithelial cells, regulates epithelial cell motility...
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28549681/a-new-cell-to-cell-interaction-model-for-epithelial-microfold-cell-formation-and-the-enhancing-effect-of-epidermal-growth-factor
#3
Puwich Chaikhumwang, Dachrit Nilubol, Angkana Tantituvanont, Pithi Chanvorachote
The formation of epithelial microfold (M) cells is mediated through cell-to-cell interactions between enterocytes and lymphocytes. Based on this concept, we developed a cell-to-cell model by encouraging interactions between enterocyte C2BBe1 and Raji B cells through a preincubation approach. Raji B cells and C2BBe1 cells were allowed to interact in detached condition for 2h at ratios of 1:1, 1:2 and 1:4 and then plated in culture plates. Monocultured C2BBe1 cells were used as the control. Flow cytometric analysis of the M cell-specific marker clusterin revealed that the optimum ratio of Raji B to C2BBe1 cells to obtain the maximum number of M cells was 1:1...
May 23, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28549347/the-roles-of-ing5-in-gliomas-a-good-marker-for-tumorigenesis-and-a-potential-target-for-gene-therapy
#4
Shuang Zhao, Zhi-Juan Zhao, Hao-Yu He, Ji-Cheng Wu, Xiao-Qing Ding, Lei Yang, Ning Jia, Zhi-Jie Li, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of ING5 on glioma cells, we overexpressed it in U87 cells, and examined the phenotypes and their relevant molecules. It was found that ING5 overexpression suppressed proliferation, energy metabolism, migration, invasion, and induced G2/M arrest, apoptosis, dedifferentiation, senescence, mesenchymal- epithelial transition and chemoresistance to cisplatin, MG132, paclitaxel and SAHA in U87 cells. There appeared a lower expression of N-cadherin, Twist, Slug, Zeb1, Zeb2, Snail, Ac-H3, Ac-H4, Cdc2, Cdk4 and XIAP, but a higher expression of Claudin 1, Histones 3 and 4, p21, p53, Bax, β-catenin, PI3K, Akt, and p-Akt in ING5 transfectants...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549259/purinergic-2x7-receptor-activation-regulates-wnt-signaling-in-human-mandibular-derived-osteoblasts
#5
Pimrumpai Rochanakit Sindhavajiva, Panunn Sastravaha, Mansuang Arksornnukit, Prasit Pavasant
OBJECTIVE: Purinergic 2X7 receptor (P2X7R) activation modulates in vitro mineralization by primary rat and human osteoblasts. However, the detailed mechanism of how P2X7R activation affects primary human osteoblasts remains unclear. The aim of this study was to investigate the effect of P2X7R activation on human mandibular-derived osteoblast (hMOB) differentiation. DESIGN: Primary human osteoblasts were obtained from non-pathologic mandibular bone from healthy patients...
May 18, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28549095/klf4-plays-an-essential-role-in-corneal-epithelial-homeostasis-by-promoting-epithelial-cell-fate-and-suppressing-epithelial-mesenchymal-transition
#6
Anil Tiwari, Chelsea L Loughner, Sudha Swamynathan, Shivalingappa K Swamynathan
Purpose: The purpose of this study was to test the hypothesis that KLF4 promotes corneal epithelial (CE) cell fate by suppressing the epithelial-mesenchymal transition (EMT), using spatiotemporally regulated CE-specific ablation of Klf4 in Klf4Δ/ΔCE (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mice. Methods: CE-specific ablation of Klf4 was achieved by feeding Klf4Δ/ΔCE mice with doxycycline chow. The wild-type (WT; normal chow-fed littermates) and the Klf4Δ/ΔCE histology was compared by hematoxylin and eosin-stained sections; EMT marker expression was quantified by quantitative PCR, immunoblots, and immunofluorescent staining; and wound healing rate was measured by CE debridement using Algerbrush...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28548956/dalbinol-a-rotenoid-from-amorpha-fruticosa-l-exerts-anti-proliferative-activity-by-facilitating-%C3%AE-catenin-degradation-in-hepatocellular-carcinoma-cells
#7
Xiaohui Zhu, Xin Wu, Jing Cheng, Hongbo Liao, Xiaoqing Di, Lili Li, Rong Li, Yanfang Zhou, Xiangning Zhang
Hepatocellular carcinoma (HCC) is a highly malignant tumor, and the main cause of treatment failure is malignant proliferation. Aberrations in Wnt/β-catenin signaling are associated with HCC development. Despite the improvements in overall survival made over the past decade from the advent of molecularly targeted therapies, these treatments do not have efficacy in all patients with different pathogeneses. Therefore, there is a demand for novel chemotherapeutic agents for HCC. To this end, we built a natural compound library and screened out a rotenoid named dalbinol from the seeds of Amorpha fruticosa L...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548936/mir-650-represses-high-risk-non-metastatic-colorectal-cancer-progression-via-inhibition-of-akt2-gsk3%C3%AE-e-cadherin-pathway
#8
Chunxian Zhou, Fengyun Cui, Jiali Li, Diyi Wang, Yingze Wei, Ying Wu, Jiping Wang, Hongguang Zhu, Shuyang Wang
Although 5-year survival rate of non-metastatic colorectal cancer (CRC) is high, about 10% of patients in stage I and II still develop into metastatic CRC and eventually die after resection. Currently, there is no effective biomarker for predicting the prognosis of non-metastatic CRC in clinical practice. In this study, we identified miR-650 as a biomarker for prognosis prediction. We observed that the expression of miR-650 in tumor tissues had a positive association with overall survival. MiR-650 inhibited cell growth and invasion in vitro and in vivo...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548834/subtly-modulating-glycogen-synthase-kinase-3-%C3%AE-allosteric-inhibitors-development-and-their-potential-for-the-treatment-of-chronic-diseases
#9
Valle Palomo, Daniel I Pérez, Carlos Roca, Cara Anderson, Natalia Rodriguez-Muela, Concepción Pérez, Jose A Morales-Garcia, Julio A Reyes, Nuria E Campillo, Ana M Pérez-Castillo, Lee L Rubin, Lubov T Timchenko, Carmen Gil, Ana Martínez
Glycogen synthase kinase 3 β (GSK-3β) is a central target in several unmet diseases. To increase the specificity of GSK-3β inhibitors in chronic treatments we are developing small molecules allowing subtle modulation of GSK-3β activity. Design synthesis, structure-activity relationships and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3β are here presented. Furthermore, we show how allosteric binders may overcome the β-catenin side effects associated to strong GSK-3β inhibition...
May 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28548306/zanthoxylum-avicennae-extract-enhances-gsk-3%C3%AE-to-attenuate-%C3%AE-catenin-via-phosphatase-2a-to-block-metastatic-effects-of-ha22t-cells-and-hepatocellular-carcinoma-xenografted-nude-mice
#10
Hsi-Chin Wu, Ing-Shiow Lay, Marthandam Asokan Shibu, Tsung-Jung Ho, Shiu-Min Cheng, Chih-Hao Lin, Tran Duc Dung, Long-Bin Jeng, Vijaya Padma Viswanadha, Chih-Yang Huang
Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/β-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on β-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay...
May 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28547742/increased-annexin-a2-and-decreased-%C3%AE-catenin-in-adenomyosis-contribute-to-adenomyosis-associated-dysmenorrhea
#11
Li Xue Liu, Yin Ga Wu, Jian Zheng
OBJECTIVE: To investigate the expression of annexin A2 (ANXA2) and β-catenin in eutopic and ectopic endometrium, and their relationships with adenomyosis-associated dysmenorrhea. METHODS: From December 2013 to June 2014, ectopic endometrium (n=30) and eutopic endometrium (n=30) of adenomyosis were collected as experimental group, and endometrium (n=30) of uterine myoma as control group from the department of gynecology and obstetrics, the affiliated hospital of Inner Mongolia medical university...
May 26, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28546515/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#12
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28546513/the-siah-e3-ubiquitin-ligases-promote-wnt-%C3%AE-catenin-signaling-through-mediating-wnt-induced-axin-degradation
#13
Lei Ji, Bo Jiang, Xiaomo Jiang, Olga Charlat, Amy Chen, Craig Mickanin, Andreas Bauer, Wenqing Xu, Xiaoxue Yan, Feng Cong
The Wnt/β-catenin signaling pathway plays essential roles in embryonic development and adult tissue homeostasis. Axin is a concentration-limiting factor responsible for the formation of the β-catenin destruction complex. Wnt signaling itself promotes the degradation of Axin. However, the underlying molecular mechanism and biological relevance of this targeting of Axin have not been elucidated. Here, we identify SIAH1/2 (SIAH) as the E3 ligase mediating Wnt-induced Axin degradation. SIAH proteins promote the ubiquitination and proteasomal degradation of Axin through interacting with a VxP motif in the GSK3-binding domain of Axin, and this function of SIAH is counteracted by GSK3 binding to Axin...
May 25, 2017: Genes & Development
https://www.readbyqxmd.com/read/28546512/wnt5a-promotes-frizzled-4-signalosome-assembly-by-stabilizing-cysteine-rich-domain-dimerization
#14
Zachary J DeBruine, Jiyuan Ke, Kaleeckal G Harikumar, Xin Gu, Peter Borowsky, Bart O Williams, Wenqing Xu, Laurence J Miller, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal "thumb" and a disulfide-stabilized C-terminal "index finger," yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD4) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers...
May 25, 2017: Genes & Development
https://www.readbyqxmd.com/read/28545972/lithium-alleviates-neurotoxic-prion-peptide-induced-synaptic-damage-and-neuronal-death-partially-by-the-upregulation-of-nuclear-target-rest-and-the-restoration-of-wnt-signaling
#15
Zhiqi Song, Wei Yang, Xiangmei Zhou, Lifeng Yang, Deming Zhao
Prion diseases are a group of infectious neurodegenerative diseases characterized by multiple neuropathological hallmarks, including accumulation of PrP(Sc), synaptic damage, and neuronal death. We previously reported that the repressor element 1-silencing transcription factor (REST), a novel neuroprotective marker in neurodegeneration, protects neurons against neurotoxic peptide (PrP106-126)-induced neurotoxicity, but fails to maintain survival following prolonged exposure to PrP106-126. Because Wnt signaling partially induces REST and is activated by lithium, we investigated the effects of lithium on REST in prion diseases...
May 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28545714/anticystogenic-activity-of-a-small-molecule-pak4-inhibitor-may-be-a-novel-treatment-for-autosomal-dominant-polycystic-kidney-disease
#16
Vicki J Hwang, Xia Zhou, Xiaonan Chen, Josephine Trott, Omran Abu Aboud, Kyuhwan Shim, Lai Kuan Dionne, Kenneth J Chmiel, William Senapedis, Erkan Baloglu, Moe R Mahjoub, Xiaogang Li, Robert H Weiss
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common hereditary renal disease with no currently available targeted therapies. Based on the established connection between β-catenin signaling and renal ciliopathies, and on data from our and other laboratories showing striking similarities of this disease and cancer, we evaluated the use of an orally bioavailable small molecule, KPT-9274 (a dual inhibitor of the protein kinase PAK4 and nicotinamide phosphoribosyl transferase), for treatment of ADPKD...
May 23, 2017: Kidney International
https://www.readbyqxmd.com/read/28545547/clonorchis-sinensis-granulin-identification-immunolocalization-and-function-in-promoting-the-metastasis-of-cholangiocarcinoma-and-hepatocellular-carcinoma
#17
Caiqin Wang, Huali Lei, Yanli Tian, Mei Shang, Yinjuan Wu, Ye Li, Lu Zhao, Mengchen Shi, Xin Tang, Tingjin Chen, Zhiyue Lv, Yan Huang, Xiaoping Tang, Xinbing Yu, Xuerong Li
BACKGROUND: Long-term infections by Clonorchis sinensis are associated with cholangitis, cholecystitis, liver fibrosis, cirrhosis, and even liver cancer. Molecules from the worm play vital roles in disease progress. In the present study, we identified and explored molecular characterization of C. sinensis granulin (CsGRN), a growth factor-like protein from C. sinensis excretory/secretory products (CsESPs). METHODS: The encoding sequence and conserved domains of CsGRN were identified and analysed by bioinformatics tools...
May 25, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28545480/effects-of-hepatitis-c-virus-core-protein-and-nonstructural-protein-4b-on-the-wnt-%C3%AE-catenin-pathway
#18
Xiao-Hua Jiang, Yu-Tao Xie, Ya-Ping Cai, Jing Ren, Tao Ma
BACKGROUND: Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. RESULTS: Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40...
May 25, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28545029/tusc3-induces-autophagy-in-human-non-small-cell-lung-cancer-cells-through-wnt-%C3%AE-catenin-signaling
#19
Yun Peng, Jun Cao, Xiao-Yi Yao, Jian-Xin Wang, Mei-Zuo Zhong, Ping-Ping Gan, Jian-Huang Li
We investigated the effects of tumor suppressor candidate 3 (TUSC3) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544579/frizzled7-antibody-functionalized-nanoshells-enable-multivalent-binding-for-wnt-signaling-inhibition-in-triple-negative-breast-cancer-cells
#20
Rachel S Riley, Emily S Day
Antibodies that antagonize cell signaling pathways specific to their targeted receptor are invaluable tools to study and treat malignancies, but their utility is limited by high production costs and treatment dosages. Researchers have shown that antibodies conjugated to nanoparticles display increased affinity for their target relative to freely delivered antibodies due to multivalency, and this study investigates how this multivalency can enable antibody-nanoparticle conjugates to inhibit oncogenic cell signaling more effectively than freely delivered antibodies...
May 22, 2017: Small
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