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Wnt beta catenin

Chun-Lu Yan, Sheng-Hua Li, Fang-Yu An, Yong-Qi Liu, Peng-Fei Xia, Zheng-Min Ma, Yan-Qiang Niu, Peng-Yao Liu
OBJECTIVES: To observe the effects of Yougui pill (Traditional Chinese Medicine) on the related factors of Wnt signal pathway of rats with knee osteoarthritis (KOA), and explore its protective mechanism. METHODS: Sixty SPF SD rats were randomly divided into the sham-operative group, model group, glucosamine sulfate group, high-dose, middle-dose, low-dose of Yougui pill treated group ( n =10). KOA model was established by modified Hulth method for six weeks. The rats in the high, middle and low-dose of Yougui pill group were treated with Yougui pills at the doses of 20,10 and 5 g/kg respectively by gastrogavage once a day for 8 weeks, while equal volume of normal saline was given to those in the sham and model control group and an equal volume of glucosamine sulfate (1...
February 8, 2018: Chinese Journal of Applied Physiology
Hong-Quan Duong, Ivan Nemazanyy, Florian Rambow, Seng Chuan Tang, Sylvain Delaunay, Lars Tharun, Alexandra Florin, Reinhard Büttner, Daniel Van Daele, Pierre Close, Jean Christophe Marine, Kateryna Shostak, Alain Chariot
MAPK signaling pathways are constitutively active in colon cancer and also promote acquired resistance to MEK1 inhibition. Here we demonstrate that BRAFV600E-mutated colorectal cancers acquire resistance to MEK1 inhibition by inducing expression of the scaffold protein CEMIP through a beta-catenin- and FRA-1-dependent pathway. CEMIP was found in endosomes and bound MEK1 to sustain ERK1/2 activation in MEK1 inhibitor-resistant BRAFV600E-mutated colorectal cancers. The CEMIP-dependent pathway maintained c-Myc protein levels through ERK1/2 and provided metabolic advantage in resistant cells, potentially by sustaining amino acids synthesis...
June 18, 2018: Cancer Research
Gaelle Spagnol, Andrew J Trease, Li Zheng, Mirtha Gutierrez, Ishika Basu, Cleofes Sarmiento, Gabriella Moore, Matthew Cervantes, Paul L Sorgen
Activation of Wnt signaling induces Connexin43 (Cx43) expression via the transcriptional activity of β-catenin, and results in the enhanced accumulation of the Cx43 protein and the formation of gap junction channels. In response to Wnt signaling, β-catenin co-localizes with the Cx43 protein itself as part of a complex at the gap junction plaque. Work from several labs have also shown indirect evidence of this interaction via reciprocal co-immunoprecipitation. Our goal for the current study was to identify whether β-catenin directly interacts with Cx43, and if so, the location of that direct interaction...
May 24, 2018: International Journal of Molecular Sciences
Kristin Teiken, Mark Kuehnel, Jan Rehkaemper, Hans Kreipe, Florian Laenger, Kais Hussein, Danny Jonigk
Post-transplant smooth muscle tumors (PTSMTs) are rare mesenchymal neoplasms which occur after solid organ or haematopoietic stem cell transplantation. PTSMT typically consist of Epstein-Barr-virus (EBV)+ smooth muscle-like cells and show an intermediate malignancy. Their main occurrences are visceral organs, especially the liver, but intracranial appearances are described and associated with a poor prognosis. EBV drives the growth of PTSMT; however, the underlying molecular mechanisms still remain unclear...
2018: Clinical Sarcoma Research
Gil Redelman-Sidi, Anna Binyamin, Isabella Gaeta, Wilhelm Palm, Craig B Thompson, Paul B Romesser, Scott W Lowe, Mukta Bagul, John G Doench, David E Root, Michael S Glickman
Macropinocytosis has emerged as an important pathway of protein acquisition in cancer cells, particularly in tumors with activated Ras such as pancreatic and colon cancer. Macropinocytosis is also the route of entry of Bacillus Calmette-Guerin (BCG) and other microbial therapies of cancer. Despite this important role in tumor biology and therapy, the full mechanisms by which cancer cells can activate macropinocytosis remain incompletely defined. Using BCG uptake to assay macropinocytosis, we executed a genome-wide shRNA screen for macropinocytosis activators and identified Wnt pathway activation as a strong driver of macropinocytosis...
June 5, 2018: Cancer Research
Qiqi Wang, Qiong Qin, Ran Song, Chunjuan Zhao, Hua Liu, Ying Yang, Siyu Gu, Deshan Zhou, Junqi He
Cervical cancer is one of the most lethal types of cancer in female. Aberrant activation of Wnt/β-catenin signaling pathway has been found to be involved in cervical cancer development and progression, whereas the underlying molecular mechanisms remain poorly understood. The present study showed that NHERF1 was a novel gene associated with both cell proliferation and Wnt signaling pathway in cervical cancer by analysis of differential gene expression and gene cluster for the cervical cancer specimens from GEO data sets...
June 4, 2018: Cell Death & Disease
Jonas Folke, Bente Pakkenberg, Tomasz Brudek
Wnt pathway is involved in synaptic plasticity and neuronal survival, and alterations in Wnt signaling have previously been reported both in aging and neurodegenerative diseases, including Alzheimer's disease (AD). This study sought to evaluate Wnt signaling pathway interplay integrity across prefrontal lobe structures in AD patients compared to normal aging. Using the open-access BrainCloud™ database, 84 gene expression profiles and clustering effect were analyzed in the dorsomedial prefrontal cortex (PFC) across a time span of 21-78 years of age...
May 26, 2018: Molecular Neurobiology
Sihuan Zhang, Han Xu, Zihong Kang, Hanfang Cai, Ruihua Dang, Chuzhao Lei, Hong Chen, Xian Guo, Xianyong Lan
Pituitary homeobox 2 (PITX2) plays crucial roles in embryogenesis, ontogenesis, growth, and development via the Wnt/beta-catenin and POU1F1 pathways. To better understand the characteristics and genetic effects of the cattle PITX2 gene, we identified alternative PITX2 splicings, examined the effects of the spliced variants on mRNA expression levels in tissues, and then used association analyses to explore the relationships between a PITX2 deletion genetic variant and growth traits in 750 native Chinese cattle...
May 22, 2018: Gene
Shujie Jiao, Yaling Liu, Yaobing Yao, Junfang Teng
Neural stem cells (NSCs) are multipotent and undifferentiated cells with the potential to differentiate into neuronal lineages and gliocytes. NSCs have the ability to generate and regenerate the brain, indicating the possibility of cell-based therapies for neurological disorders. miR-124 has been demonstrated as a modulator in the survival, expansion, and differentiation of NSCs. However, the underlying molecular mechanisms of miR-124 in NSC development are still far from being understood. The expressions of miR-124, dishevelled binding antagonist of beta-catenin 1 (DACT1), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), β-catenin, cyclinD1, and glycogen synthase kinase-3β (GSK-3β) were examined by qRT-PCR or western blot...
May 21, 2018: Molecular and Cellular Biochemistry
Haixia Huang, Mingxing Zhang, Meng Zhang, Jing Peng, Guiling Li, Congjian Xu, Suiqi Gui
ETHNOPHARMACOLOGICAL RELEVANCE: Pinellia pedatisecta Schott extract (PE), a traditional Chinese medicine, has been used to reduce swelling, dry dampness and suppress cervical tumors. AIMS: To evaluate the roles of PE in the regulation of anti-tumor effects and the cellular immune response in the tumor microenvironment. METHODS: The immune microenvironment of HPV+ TC-1 tumors was examined by immunohistochemistry, real-time PCR and flow cytometry...
May 18, 2018: Journal of Ethnopharmacology
Fengyun Yu, Leilei Bing, Yanrong Xie, Wenjuan Yu
BACKGROUND: Dysfunction of pancreatic beta cells is related with type 2 diabetes mellitus. Dioscin, a natural steroid saponin, has many pharmacological effects. The aim of this study was to investigate the effects of dioscin on apoptosis of pancreatic beta cells induced by high glucose. METHODS: Pancreatic cell line RNAKT-15 was treated with 20 mM glucose with or without different concentrations of dioscin and viability and apoptosis of cells were measured. Western blot assay was used to measure the expression levels of some proteins such as phosphorylated glycogen synthase kinase 3β (GSK-3β) and β-catenin...
May 1, 2018: Clinical Laboratory
Zongbing Guo, Zhenzhen Liu, Haifeng Yue, Jingyuan Wang
Colorectal carcinoma is a common malignant tumor occurring in the alimentary system. Despite developments of modern medicine, developed resistance to 5-fluorouracil (5-FU) may lead to poor prognosis. Herein, we aimed to explore the effects of beta-elemene on colorectal carcinoma cells (HCT116 and HT29) as well as the underlying mechanisms. Beta-elemene reduced cell viability and induced apoptosis in HCT116 and HT29 cells. Increased apoptosis following beta-elemene exposure was due to enhanced sensitivity to 5-FU through down-regulating miR-191...
May 8, 2018: Journal of Cellular Biochemistry
Mark Lipphardt, Hassan Dihazi, Noo Li Jeon, Sina Dadafarin, Brian B Ratliff, David W Rowe, Gerhard A Müller, Michael S Goligorsky
Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-β) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants...
May 3, 2018: Nephrology, Dialysis, Transplantation
John Rieth, Subbaya Subramanian
An increased understanding of the interactions between the immune system and tumors has opened the door to immunotherapy for cancer patients. Despite some success with checkpoint inhibitors including ipilimumab, pembrolizumab, and nivolumab, most cancer patients remain unresponsive to such immunotherapy, likely due to intrinsic tumor resistance. The mechanisms most likely involve reducing the quantity and/or quality of antitumor lymphocytes, which ultimately are driven by any number of developments: tumor mutations and adaptations, reduced neoantigen generation or expression, indoleamine 2,3-dioxygenase (IDO) overexpression, loss of phosphatase and tensin homologue (PTEN) expression, and overexpression of the Wnt⁻β-catenin pathway...
May 2, 2018: International Journal of Molecular Sciences
Brooke N Nakamura, Alison Glazier, Michael G Kattah, Bao Duong, Yanxia Jia, Daniel Campo, Ling Shao
A20 is a ubiquitin-editing enzyme that is known to regulate inflammatory signaling and cell death. However, A20 mutations are also frequently found in multiple malignancies suggesting a potential role as a tumor suppressor as well. We recently described a novel role for A20 in regulating the wnt-beta-catenin signaling pathway and suppressing colonic tumor development in mice. The underlying mechanisms for this phenomenon are unclear. To study this, we first generated A20 knockout cell lines by genome-editing techniques...
2018: PloS One
Arun Sharma, Yuan Zhang, Jan W Buikema, Vahid Serpooshan, Orlando Chirikian, Nina Kosaric, Jared M Churko, Elda Dzilic, Alice Shieh, Paul W Burridge, Joseph C Wu, Sean M Wu
Bioactive lipids such as sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) regulate diverse processes including cell proliferation, differentiation, and migration. However, their roles in cardiac differentiation and cardiomyocyte proliferation have not been explored. Using a 96-well differentiation platform for generating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) we found that S1P and LPA can independently enhance cardiomyocyte generation when administered at an early stage of differentiation...
April 26, 2018: Scientific Reports
Jiaojie Hui, Jianping Zhang, Mengjia Pu, Xingliang Zhou, Liang Dong, Xuqiang Mao, Guofeng Shi, Jian Zou, Jingjing Wu, Dongmei Jiang, Guangjun Xi
Background: It is widely accepted that cognitive processes, such as learning and memory, are affected in depression, but the molecular mechanisms underlying the interactions of these 2 disorders are not clearly understood. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to play an important role in the regulation of learning and memory. Methods: The present study used a rat model of depression, chronic unpredictable stress, to determine whether hippocampal GSK-3β/β-catenin signaling was involved in learning and memory alterations...
April 23, 2018: International Journal of Neuropsychopharmacology
Weijuan Shao, Vivian Szeto, Zhuolun Song, Lili Tian, Zhong-Ping Feng, M Cristina Nostro, Tianru Jin
Pancreatic β-cell Tcf7l2 deletion or its functional knockdown suggested the essential role of this Wnt pathway effector in controlling insulin secretion, glucose homeostasis and β-cell gene expression. As the LIM homeodomain protein ISL1 is a suggested Wnt pathway downstream target, we hypothesize that it mediates metabolic functions of TCF7L2. We aimed to determine the role of ISL1 in mediating the function of TCF7L2 and the incretin hormone GLP-1 in pancreatic β-cells. The effect of dominant negative TCF7L2 (TCF7L2DN) mediated Wnt pathway functional knockdown on Isl1 expression was determined in βTCFDN mouse islets and in the rat insulinoma cell line INS-1 832/13...
July 2018: Journal of Molecular Endocrinology
B I Gomez, B H Aloqaily, C A Gifford, D M Hallford, J A Hernandez Gifford
Appreciation of mechanisms that affect steroidogenesis is critical to identifying compromising signals that may decrease reproductive efficiency. Follicle maturation and steroidogenesis requires coordinated actions from the pituitary gonadotropins, and local ovarian signaling molecules. Beta-catenin (CTNNB1), the lynchpin molecule of canonical wingless-type mouse mammary tumor virus integration site (WNT) signaling is required for maximal gonadotropin stimulation of steroid production from granulosa (GC) and luteal cells...
April 13, 2018: Journal of Animal Science
Ji Young Kim, Jae Souk Lee, Hyun Sub Hwang, Dongjin R Lee, Chul-Yong Park, Sung Jun Jung, Young Rang You, Dae-Sung Kim, Dong-Wook Kim
The canonical Wnt signal pathway plays a pivotal role in anteroposterior patterning and midbrain specification during early neurogenesis. Activating Wnt signal has been a strategy for differentiating human pluripotent stem cells (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular mechanism(s) of how the Wnt signal drives posterior fate remained unclear. In this study, we found that activating the canonical Wnt signal significantly upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells (NPCs)...
April 13, 2018: Experimental & Molecular Medicine
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