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Wnt/b-catenin signal

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https://www.readbyqxmd.com/read/28651950/the-loss-of-kr%C3%A3-ppel-like-factor-15-in-foxd1-stromal-cells-exacerbates-kidney-fibrosis
#1
Xiangchen Gu, Sandeep K Mallipattu, Yiqing Guo, Monica P Revelo, Jesse Pace, Timothy Miller, Xiang Gao, Mukesh K Jain, Agnieszka B Bialkowska, Vincent W Yang, John C He, Changlin Mei
Large epidemiological studies clearly demonstrate that multiple episodes of acute kidney injury contribute to the development and progression of kidney fibrosis. Although our understanding of kidney fibrosis has improved in the past two decades, we have limited therapeutic strategies to halt its progression. Myofibroblast differentiation and proliferation remain critical to the progression of kidney fibrosis. Although canonical Wnt signaling can trigger the activation of myofibroblasts in the kidney, mediators of Wnt inhibition in the resident progenitor cells are unclear...
June 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28639895/upregulation-of-mir-199a-b-contributes-to-cisplatin-resistance-via-wnt-%C3%AE-catenin-abcg2-signaling-pathway-in-aldha1-colorectal-cancer-stem-cells
#2
Binghe Chen, Dezhong Zhang, Jun Kuai, Mingkun Cheng, Xiangjie Fang, Guangyan Li
Cisplatin resistance in colorectal cancer largely results from the colorectal cancer stem cells which could be targeted to improve the efficacy of chemotherapy. MicroRNAs are possible modulators of cancer stem cell characteristics and maybe involved in the retention of cancer stem cell chemoresistance. The aim of this study was to investigate the biological function of miR-199a/b on cisplatin resistance in colorectal cancer stem cells and its related mechanisms. Here, ALDHA1(+) cells from primary colorectal cancer tissues behaved similar to cancer stem cells and were chemoresistant to cisplatin...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28625128/the-wnt-%C3%AE-catenin-signalling-pathway-inhibitor-sclerostin-is-a-biomarker-for-early-atherosclerosis-in-obesity
#3
Djordje S Popovic, Milena Mitrovic, Dragana Tomic-Naglic, Tijana Icin, Ivana Bajkin, Bojan Vukovic, Damir Benc, Zeljko Zivanovic, Branka Kovacev-Zavisic, Edita Stokic
BACKGROUND: Sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/β-catenin signalling pathway (WβcSP), which plays an important role in bone metabolism and in vascular biology. It could act protective regarding atherosclerosis development through its effect on WβcSP in vascular cells. Nevertheless, results of studies analyzing association between circulating sclerostin level (CSL) and atherosclerotic diseases (AD) are showing conflicting results...
June 18, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28624869/incorporation-of-cerium-oxide-into-hydroxyapatite-coating-protects-bone-marrow-stromal-cells-against-h2o2-induced-inhibition-of-osteogenic-differentiation
#4
Kai Li, Qingyi Shen, Youtao Xie, Mingyu You, Liping Huang, Xuebin Zheng
Oxidative stress exerts a key influence in osteoporosis in part by inhibiting osteogenic differentiation of bone marrow stromal cells (BMSCs). With their unique antioxidant properties and reported biocompatibility, cerium oxide (CeO2) ceramics exhibit promising potential for the treatment of osteoporosis resulting from oxidative stress. In this study, protective effects of CeO2-incorporated hydroxyapatite coatings (HA-10Ce and HA-30Ce) on the viability and osteogenic differentiation of H2O2-treated BMSCs were examined...
June 17, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28611108/wnt-%C3%AE-catenin-signaling-contributes-to-tumor-malignancy-and-is-targetable-in-gastrointestinal-stromal-tumor
#5
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Michael J Cavnar, Teresa S Kim, Vinod P Balachandran, Juan A Santamaria-Barria, Noah A Cohen, Michael J Beckman, Benjamin Medina, Ferdinand Rossi, Megan H Crawley, Jennifer K Loo, Joanna H Maltbaek, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. While the Wnt/b-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed b-catenin and contained active, dephosphorylated nuclear b-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28600813/elucidation-of-altered-pathways-in-tumor-initiating-cells-of-triple-negative-breast-cancer-a-useful-cell-model-system-for-drug-screening
#6
Anne G Christensen, Sidse Ehmsen, Mikkel G Terp, Richa Batra, Nicolas Alcaraz, Jan Baumbach, Julie B Noer, José Moreira, Rikke Leth-Larsen, Martin R Larsen, Henrik J Ditzel
A limited number of cancer cells within a tumor are thought to have self-renewing and tumor-initiating capabilities that produce the remaining cancer cells in a heterogeneous tumor mass. Elucidation of central pathways preferentially used by tumor-initiating cells/cancer stem cells (CSCs) may allow their exploitation as potential cancer therapy targets. We used single cell cloning to isolate and characterize four isogenic cell clones from a triple-negative breast cancer cell line; two exhibited mesenchymal-like and two epithelial-like characteristics...
June 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28600477/targeting-the-wnt-pathway-and-cancer-stem-cells-with-anti-progastrin-humanized-antibodies-a-major-breakthrough-for-k-ras-mutated-colorectal-cancer-treatment
#7
Alexandre Prieur, Monica Cappellini, Guillaume Habif, Marie-Paule Lefranc, Thibault Mazard, Eric Morency, Jean-Marc Pascussi, Maud Flaceliere, Nathalie Cahuzac, Berengere Vire, Benjamin Dubuc, Amandine Durochat, Pierre Liaud, Jérémy Ollier, Caroline Pfeiffer, Sophie Poupeau, Véronique Saywell, Chris Planque, Eric Assenat, Frédéric Bibeau, Jean-François Bourgaux, Pascal Pujol, Alain Sézeur, Marc Ychou, Dominique Joubert
<p>Patients with metastatic colorectal cancer (CRC) suffer from disease relapse mainly due to cancer stem cells (CSC). Interestingly, they have an increased level of blood progastrin, a tumor-promoting peptide essential for the self-renewal of colon CSCs, which is also a direct b-catenin/Tcf4 target gene. In this study we aimed to develop a novel targeted therapy to neutralize secreted progastrin in order to inhibit Wnt signaling, CSCs and reduce relapses.</p> Experimental Design: <p>Antibodies (monoclonal and humanized) directed against progastrin were produced and selected for target specificity and affinity...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28592538/identification-of-il-27-il-27ra-as-a-critical-immune-axis-for-in-vivo-hiv-control
#8
M Ruiz-Riol, D Berdnik, A Llano, B Mothe, C Gálvez, S Pérez-Álvarez, B Oriol-Tordera, A Olvera, S Silva-Arrieta, Michael Meulbroek, Ferran Pujol, J Coll, J Martinez-Picado, C Ganoza, J Sanchez, G Gómez, T Wyss-Coray, C Brander
Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray able to measure >600 plasma proteins involved in cell-to-cell communication was used to measure plasma protein profiles in 96 HIV-infected, treatment-naïve individuals with high (>50,000) or low (<10,000 HIV RNA copies/ml) viral loads...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28578904/role-of-ras-wnt-%C3%AE-catenin-axis-activation-in-the-pathogenesis-of-podocyte-injury-and-tubulo-interstitial-nephropathy
#9
Lin Chen, Dan-Qian Chen, Ming Wang, Dan Liu, Hua Chen, Fang Dou, Nosratola D Vaziri, Ying-Yong Zhao
Renin-angiotensin system (RAS) plays a key role in the development and progression of chronic kidney disease (CKD). Recent studies have demonstrated activation of Wnt/β-catenin pathway by RAS in CKD. However, the underlying mechanisms of RAS and Wnt/β-catenin signaling interaction and their contribution to the pathogenesis of CKD have not been fully elucidated. Present study is designed to investigate the role of RAS/Wnt/β-catenin axis activation in tubulo-interstitial fibrosis and glomerulosclerosis by the cultured HK-2 and podocytes...
June 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28559284/the-autism-linked-ube3a-t485a-mutant-e3-ubiquitin-ligase-activates-the-wnt-%C3%AE-catenin-pathway-by-inhibiting-the-proteasome
#10
Jason J Yi, Smita R Paranjape, Matthew P Walker, Rajarshi Choudhury, Justin M Wolter, Giulia Fragola, Michael J Emanuele, Michael B Major, Mark J Zylka
UBE3A is a HECT domain E3 ubiquitin ligase whose dysfunction is linked to autism, Angelman syndrome, and cancer. Recently, we characterized a de novo autism-linked UBE3A mutant (UBE3AT485A) that disrupts phosphorylation control of UBE3A activity. Through quantitative proteomics and reporter assays, we found that the UBE3AT485A protein ubiquitinates multiple proteasome subunits, reduces proteasome subunit abundance and activity, stabilizes nuclear β-catenin, and stimulates canonical Wnt signaling more effectively than wild-type UBE3A...
May 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28553956/autocrine-wnt2-signaling-in-fibroblasts-promotes-colorectal-cancer-progression
#11
N Kramer, J Schmöllerl, C Unger, H Nivarthi, A Rudisch, D Unterleuthner, M Scherzer, A Riedl, M Artaker, I Crncec, D Lenhardt, T Schwarz, B Prieler, X Han, M Hengstschläger, J Schüler, R Eferl, R Moriggl, W Sommergruber, H Dolznig
The canonical WNT signaling pathway is crucial for intestinal stem cell renewal and aberrant WNT signaling is an early event in colorectal cancer (CRC) development. Here, we show for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma. The impact of stromal WNT2 on carcinoma formation or progression was not addressed so far. Canonical WNT/β-catenin signaling was assessed using a 7TGP-reporter construct. Furthermore, effects of WNT2 on fibroblast migration and invasion were determined using siRNA-mediated gene silencing...
May 29, 2017: Oncogene
https://www.readbyqxmd.com/read/28543818/bone-formation-is-coupled-to-resorption-via-suppression-of-sclerostin-expression-by-osteoclasts
#12
Masanori Koide, Yasuhiro Kobayashi, Teruhito Yamashita, Shunsuke Uehara, Midori Nakamura, B Yukihiro Hiraoka, Yuki Ozaki, Tadahiro Iimura, Hisataka Yasuda, Naoyuki Takahashi, Nobuyuki Udagawa
Bone formation is coupled to bone resorption throughout life. However, the coupling mechanisms are not fully elucidated. Using Tnfrsf11b-deficient (OPG(-/-) ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/β-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures...
May 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28509806/advances-in-management-of-hepatocellular-carcinoma
#13
Manon Allaire, Jean-Charles Nault
PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is one of the leading causes of death by cancer worldwide due to a dismal prognosis. The aim of this review is to summarize the main advances in the pathophysiology and management of HCC. RECENT FINDINGS: Genomic analysis has recently delineated the key signaling pathways aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/β-catenin, epigenetic modifier, oxidative stress etc.). Major advances in the clinical care of patients with HCC are helping to refine the diagnosis algorithm and tumor staging...
July 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28506997/the-phosphatase-pgam5-antagonizes-wnt-%C3%AE-catenin-signaling-in-embryonic-anterior-posterior-axis-patterning
#14
Verena Rauschenberger, Dominic B Bernkopf, Sabrina Krenn, Kowcee Jalal, Jens Heller, Jürgen Behrens, Marc Gentzel, Alexandra Schambony
The scaffold protein Dishevelled is a central intracellular component of Wnt signaling pathways. Various kinases have been described that regulate and modulate Wnt signaling through phosphorylation of Dishevelled. However, besides general protein phosphatases 1 and 2 (PP1 and PP2), no specific protein phosphatases have been identified. Here, we report on the identification and functional characterization of the protein phosphatase Pgam5 in vitro and in vivo in Xenopus Pgam5 is a novel antagonist of Wnt/β-Catenin signaling in human cells and Xenopus embryogenesis...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28506911/mangiferin-protects-against%C3%A2-%C3%A2-intestinal-ischemia-reperfusion-induced-%C3%A2-liver-injury-%C3%A2-%C3%A2-involvement-of-ppar-%C3%A2-%C3%AE-gsk-3%C3%AE-and-wnt-%C3%AE-catenin-pathway%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2
#15
Shorouk M El-Sayyad, Ayman A Soubh, Azza S Awad, Hanan S El-Abhar
AIM: Mangiferin (MF), a xanthonoid from Mangifera indica, possesses anti-inflammatory, immunomodulatory, and potent antioxidant effects; however, its protective effect against mesenteric ischemia/reperfusion (I/R)-induced liver injury has not been fully clarified. The study was designed to assess the possible mechanism of action of MF against mesenteric I/R model. MAIN METHODS: Male Wister rats were treated with MF (20mg/kg, i.p) or the vehicle for 3 days before I/R, which was induced by clamping the superior mesenteric artery for 30min followed by declamping for 60min...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28500952/isolation-and-characterization-of-lymphoid-enhancer-factor-1-positive-deciduous-dental-pulp-stem-like-cells-after-transfection-with-a-piggybac-vector-containing-lef1-promoter-driven-selection-markers
#16
Tomoya Murakami, Issei Saitoh, Masahiro Sato, Emi Inada, Miki Soda, Masataka Oda, Hisanori Domon, Yoko Iwase, Tadashi Sawami, Kazunari Matsueda, Yutaka Terao, Hayato Ohshima, Hirofumi Noguchi, Haruaki Hayasaki
OBJECTIVE: Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein that is expressed in pre-B and T cells. LEF1 is also an important member of the Wnt/β-catenin signaling pathway that plays important roles in the self-renewal and differentiation of embryonic stem cells. We speculated that LEF1 might function in the stem cells from human exfoliated deciduous teeth (SHED). In this study, we attempted to isolate such LEF1-positive cells from human deciduous dental pulp cells (HDDPCs) by genetic engineering technology, using the human LEF1 promoter...
May 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28495756/cystic-fibrosis-transmembrane-conductance-regulator-mediates-tenogenic-differentiation-of-tendon-derived-stem-cells-and-tendon-repair-accelerating-tendon-injury-healing-by-intervening-in-its-downstream-signaling
#17
Yang Liu, Jia Xu, Liangliang Xu, Tianyi Wu, Yuxin Sun, Yuk-Wai Lee, Bin Wang, Hsiao-Chang Chan, Xiaohua Jiang, Jinfang Zhang, Gang Li
Tendons are a mechanosensitive tissue, which enables them to transmit to bone forces that are derived from muscle. Patients with tendon injuries, such as tendinopathy or tendon rupture, were often observed with matrix degeneration, and the healing of tendon injuries remains a challenge as a result of the limited understanding of tendon biology. Our study demonstrates that the stretch-mediated activation channel, cystic fibrosis transmembrane conductance regulator (CFTR), was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic differentiation under mechanical stretching...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28476031/new-tumor-suppressor-micrornas-target-glypican-3-in-human-liver-cancer
#18
Flora Cartier, Emilie Indersie, Sarah Lesjean, Justine Charpentier, Katarzyna B Hooks, Amani Ghousein, Angélique Desplat, Nathalie Dugot-Senant, Véronique Trézéguet, Francis Sagliocco, Martin Hagedorn, Christophe F Grosset
Glypican-3 (GPC3) is an oncogene, frequently upregulated in liver malignancies such as hepatocellular carcinoma (HCC) and hepatoblastoma and constitutes a potential molecular target for therapy in liver cancer. Using a functional screening system, we identified 10 new microRNAs controlling GPC3 expression in malignant liver cells, five of them e.g. miR-4510, miR-203a-3p, miR-548aa, miR-376b-3p and miR-548v reduce GPC3 expression. These 5 microRNAs were significantly downregulated in tumoral compared to non-tumoral liver and inhibited tumor cell proliferation...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28472810/the-long-non-coding-rna-crnde-promotes-colorectal-carcinoma-progression-by-competitively-binding-mir-217-with-tcf7l2-and-enhancing-the-wnt-%C3%AE-catenin-signaling-pathway
#19
Bo Yu, Xuan Ye, Qiong Du, Bin Zhu, Qing Zhai, Xin-Xiang Li
BACKGROUND/AIMS: The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. METHODS: Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28467820/non-equivalence-of-wnt-and-r-spondin-ligands-during-lgr5-intestinal-stem-cell-self-renewal
#20
Kelley S Yan, Claudia Y Janda, Junlei Chang, Grace X Y Zheng, Kathryn A Larkin, Vincent C Luca, Luis A Chia, Amanda T Mah, Arnold Han, Jessica M Terry, Akifumi Ootani, Kelly Roelf, Mark Lee, Jenny Yuan, Xiao Li, Christopher R Bolen, Julie Wilhelmy, Paige S Davies, Hiroo Ueno, Richard J von Furstenberg, Phillip Belgrader, Solongo B Ziraldo, Heather Ordonez, Susan J Henning, Melissa H Wong, Michael P Snyder, Irving L Weissman, Aaron J Hsueh, Tarjei S Mikkelsen, K Christopher Garcia, Calvin J Kuo
The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands...
May 11, 2017: Nature
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