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Wnt beta catenin

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https://www.readbyqxmd.com/read/28334814/genome-wide-association-study-identifies-novel-susceptible-loci-and-highlights-wnt-beta-catenin-pathway-in-the-development-of-adolescent-idiopathic-scoliosis
#1
Zezhang Zhu, Leilei Xu, Nelson Leung-Sang Tang, Xiaodong Qin, Zhenhua Feng, Weixiang Sun, Weiguo Zhu, Benlong Shi, Peng Liu, Saihu Mao, Jun Qiao, Zhen Liu, Xu Sun, Fangcai Li, Jack Chun-Yiu Cheng, Yong Qiu
The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1...
February 28, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28298922/interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway-in-type-2-diabetes-and-colon-cancer
#2
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
In both colon cancer and type 2 diabetes, metabolic changes induced by upregulation of the Wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) may help account for the frequent association of these two diseases. In both diseases, PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated. In colon cancer, upregulation of the canonical Wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex...
2017: PPAR Research
https://www.readbyqxmd.com/read/28293067/syndecan-1-acts-as-an-important-regulator-of-cxcl1-expression-and-cellular-interaction-of-human-endometrial-stromal-and-trophoblast-cells
#3
Dunja Maria Baston-Buest, Olga Altergot-Ahmad, Sarah Jean Pour, Jan-Steffen Krüssel, Udo Rudolf Markert, Tanja Natascha Fehm, Alexandra Petra Bielfeld
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28293052/beta-catenin-forms-protein-aggregation-at-high-concentrations-in-hek293tcells
#4
Marie Saghaeian Jazi, Seyed Mahmoud Arab Najafi
BACKGROUND: The canonical Wnt signal transduction (or the Wnt/β-catenin pathway) plays a crucial role in the development of animals and in carcinogenesis. Beta-catenin is the central component of this signaling pathway. The activation of Wnt/β-catenin signaling results in the cytoplasmic and nuclear accumulation of β-catenin. In the nucleus, β-catenin interacts with the TCF/LEF transcription factors and, therefore, participates in the upregulation or downregulation of some important genes involved in diverse cellular activities...
January 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in-vitro-and-in-mice-by-inhibiting-cdc37-signaling
#5
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
March 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28271698/ovarian-cancer-in-endometriosis-clinical-and-molecular-aspects-an-update
#6
Rachel Ruderman, Mary E Pavone
While endometriosis is a benign condition, the presence of endometriosis has been associated with the development of several types of cancers, including ovarian. Endometriomas, or ovarian endometriotic cysts, are found in 17-44% of patients with endometriosis, and may be a common precursor lesions to ovarian cancer. Endometriosis associated ovarian cancer is especially prominent in endometrioid and clear cell ovarian tumor histological subtypes. Several common pathways linking endometriosis and ovarian cancer have been elucidated, including the dominance of certain cytokines, oxidative stress, and a hyper-estrogenic hormonal milieu, which propagate both endometriosis and endometriosis associated ovarian cancer...
March 7, 2017: Minerva Ginecologica
https://www.readbyqxmd.com/read/28244852/silencing-transmembrane-protein-45b-tnem45b-inhibits-proliferation-invasion-and-tumorigenesis-in-osteosarcoma-cells
#7
(no author information available yet)
Transmembrane protein 45B (TMEM45B) is a member of TMEMs and has been reported to be expressed abnormally in differentkinds of human tumors. However, the biological function of TMEM45B in osteosarcoma remains unclear. The objective of this study was to investigate the role of TMEM45B in regulating the biological behavior of osteosarcoma cells. Oure results demonstrated that the expression of TMEM45B at both protein and mRNA levels was dramatically up-regulated human osteosarcoma cell lines. Knockdown of TMEM45B significantly suppressed the proliferation, migration and invasion of U2OS cells <em>in vitro</em>...
December 21, 2016: Oncology Research
https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#8
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28223363/auto-inhibition-of-dishevelled-regulated-by-its-extreme-c-terminus-plays-a-distinct-role-in-wnt-beta-catenin-and-wnt-pcp-signaling-pathways
#9
Jing Qi, Ho-Jin Lee, Audrey Saquet, Xiao-Ning Cheng, Ming Shao, Jie J Zheng, De-Li Shi
Dishevelled (Dvl) is a key intracellular signaling molecule that mediates the activation of divergent Wnt pathways. It contains three highly conserved domains known as DIX, PDZ and DEP, whose functions in beta-catenin-dependent canonical Wnt and beta-catenin-independent non-canonical Wnt signaling have been well characterized. The C-terminal region is also highly conserved from invertebrates to vertebrates. However, its function in regulating the activation of different Wnt signals remains unclear. We previously reported that Dvl conformational change triggered by the highly conserved PDZ-binding C-terminus is important for the pathway specificity...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28217097/feedback-activation-of-basic-fibroblast-growth-factor-signaling-via-the-wnt-%C3%AE-catenin-pathway-in-skin-fibroblasts
#10
Xu Wang, Yuting Zhu, Congcong Sun, Tao Wang, Yingjie Shen, Wanhui Cai, Jia Sun, Lisha Chi, Haijun Wang, Na Song, Chao Niu, Jiayi Shen, Weitao Cong, Zhongxin Zhu, Yuanhu Xuan, Xiaokun Li, Litai Jin
Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28191283/active-%C3%AE-catenin-is-regulated-by-the-pten-pi3-kinase-pathway-a-role-for-protein-phosphatase-pp2a
#11
Amit Persad, Geetha Venkateswaran, Li Hao, Maria E Garcia, Jenny Yoon, Jaskiran Sidhu, Sujata Persad
Dysregulation of Wnt/β-catenin signaling has been associated with the development and progression of many cancers. The stability and subcellular localization of β-catenin, a dual functional protein that plays a role in intracellular adhesion and in regulating gene expression, is tightly regulated. However, little is known about the transcriptionally active form of β-catenin, Active Beta Catenin (ABC), that is unphosphorylated at serine 37 (Ser37) and threonine 41 (Thr41). Elucidating the mechanism by which β-catenin is activated to generate ABC is vital to the development of therapeutic strategies to block β-catenin signaling for cancer treatment...
November 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28186678/gamma-secretase-inhibitor-ix-gsi-impairs-concomitant-activation-of-notch-and-wnt-beta-catenin-pathways-in-cd44-gastric-cancer-stem-cells
#12
Samarpita Barat, Xi Chen, Khac Cuong Bui, Przemyslaw Bozko, Julian Götze, Matthias Christgen, Till Krech, Nisar P Malek, Ruben R Plentz
Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44(+) CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28152305/concurrent-hypermethylation-of-sfrp2-and-dkk2-activates-the-wnt-%C3%AE-catenin-pathway-and-is-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#13
Hao Wang, Xiang-Long Duan, Xiao-Li Qi, Lei Meng, Yi-Song Xu, Tong Wu, Peng-Gao Dai
Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28143772/stearoyl-coa-desaturase-promotes-liver-fibrosis-and-tumor-development-in-mice-via-a-wnt-positive-signaling-loop-by-stabilization-of-low-density-lipoprotein-receptor-related-proteins-5-and-6
#14
Keane K Y Lai, Soo-Mi Kweon, Feng Chi, Edward Hwang, Yasuaki Kabe, Reiichi Higashiyama, Lan Qin, Rui Yan, Raymond P Wu, Naoaki Fujii, Samuel French, Jun Xu, Jian-Ying Wang, Ramanchadran Murali, Lopa Mishra, Ju-Seog Lee, James M Ntambi, Hidekazu Tsukamoto
BACKGROUND & AIMS: Stearoyl-CoA desaturase (SCD) synthesizes monounsaturated fatty acids (MUFAs) and has been associated with development of metabolic syndrome, tumorigenesis, and stem cell characteristics. We investigated whether and how SCD promotes liver fibrosis and tumor development in mice. METHODS: Rodent primary hepatic stellate cells (HSCs), mouse liver tumor-initiating stem cell-like cells (TICs), and human hepatocellular carcinoma (HCC) cell lines were exposed to Wnt signaling inhibitors and changes in gene expression patterns were analyzed...
January 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28123643/gsk3%C3%AE-activity-is-essential-for-senescence-associated-heterochromatin-foci-sahf-formation-induced-by-hmga2-in-wi38-cells
#15
Xi Shi, Baoqing Tian, Chi Ma, Lingxia Liu, Na Zhang, Yuan Na, Jing Li, Jun Lu, Yuehua Qiao
Cellular senescence is an irreversible form of cell cycle arrest, which is often characterized by domains of facultative heterochromatin substructures also known as senescence-associated heterochromatin foci (SAHF). SAHF assembly is likely mediated through the downregulation of the Wnt pathway, which inhibits Glycogen Synthase Kinase 3 Beta (GSK3β) in cells undergoing replicative senescence. Alternatively, High Mobility Group AT-Hook 2 (HMGA2) can also induce SAHF formation in primary cells, through a process in which the involved cell signaling pathway is unknown...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28119087/rap1b-a-dvl2-binding-protein-activates-wnt-beta-catenin-signaling-in-esophageal-squamous-cell-carcinoma
#16
Zhao Jia, Yang Yang, Zhu Dengyan, Zhang Chunyang, Liu Donglei, Wu Kai, Zhao Song
RAP1B is a small GTPase, which regulates multiple cellular processes. Up-regulation of RAP1B has been observed in several cancer types. Although previous study has shown that miR-518 inhibited the proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells possibly by targeting RAP1B, the expression pattern and the functions of RAP1B in ESCC are not fully understood. Here, we have fund that the expression of RAP1B was up-regulated in ESCC clinical samples. Gain-of-function and loss-of-function assays demonstrated that RAP1B promoted the growth, migration and metastasis of the ESCC cells...
January 21, 2017: Gene
https://www.readbyqxmd.com/read/28100625/the-ptpn14-tumor-suppressor-is-a-degradation-target-of-human-papillomavirus-e7
#17
Anita Szalmás, Vjekoslav Tomaić, Om Basukala, Paola Massimi, Suruchi Mittal, József Kónya, Lawrence Banks
Activation of signaling pathways ensuring cell growth is essential for the proliferative competence of human papillomavirus (HPV)-infected cells. Tyrosine kinases and phosphatases are key regulators of cellular growth control pathways. A recently identified potential cellular target of HPV E7 is the cytoplasmic protein tyrosine phosphatase PTPN14, which is a potential tumor suppressor and is linked to the control of the Hippo and Wnt/beta-catenin signaling pathways. In this study, we show that the E7 proteins of both high-risk and low-risk mucosal HPV types can interact with PTPN14...
April 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#18
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28054444/heterozygous-pathogenic-variant-in-dact1-causes-an-autosomal-dominant-syndrome-with-features-overlapping-townes-brocks-syndrome
#19
Bryn D Webb, Sanjeeva Metikala, Patricia G Wheeler, Mingma D Sherpa, Sander M Houten, Marko E Horb, Eric E Schadt
A heterozygous nonsense variant was identified in dapper, antagonist of beta-catenin, 1 (DACT1) via whole-exome sequencing in family members with imperforate anus, structural renal abnormalities, genitourinary anomalies, and/or ear anomalies. The DACT1 c.1256G>A;p.Trp419(*) variant segregated appropriately in the family consistent with an autosomal dominant mode of inheritance. DACT1 is a member of the Wnt-signaling pathway, and mice homozygous for null alleles display multiple congenital anomalies including absent anus with blind-ending colon and genitourinary malformations...
April 2017: Human Mutation
https://www.readbyqxmd.com/read/28043904/liver-cancer-cell-of-origin-molecular-class-and-effects-on%C3%A2-patient-prognosis
#20
REVIEW
Daniela Sia, Augusto Villanueva, Scott L Friedman, Josep M Llovet
Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis and clarify the classes of liver cancer based on molecular features and how they affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis...
December 30, 2016: Gastroenterology
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