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https://www.readbyqxmd.com/read/29114927/genetic-study-of-non-syndromic-tooth-agenesis-through-the-screening-of-paired-box-9-msh-homeobox-1-axin-2-and-wnt-family-member-10a-genes-a-case-series
#1
Marwa Haddaji Mastouri, Peter De Coster, Aicha Zaghabani, Frej Jammali, Nabiha Raouahi, Amina Ben Salem, Ali Saad, Paul Coucke, Dorra H'mida Ben Brahim
Non-syndromic tooth agenesis (NSTA) is the most common developmental anomaly in humans. Several studies have been conducted on dental agenesis and numerous genes have been identified. However, the pathogenic mechanisms responsible for NSTA are not clearly understood. We studied a group of 28 patients with sporadic NSTA and nine patients with a family history of tooth agenesis. We focused on four genes - paired box 9 (PAX9), Wnt family member 10A (WNT10A), msh homeobox 1 (MSX1), and axin 2 (AXIN2) - using direct Sanger sequencing of the exons and intron-exon boundaries...
November 8, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/29098832/-effect-of-aralia-echinocaulis-containing-serum-on-wnt-%C3%AE-catenin-signaling-pathway-of-primary-osteoblast
#2
Xiang-Jiao Yi, Jin-Cheng Li, Song-Yue Wang, Meng-Yun Yan, Jian Cui, Ling-Peng Pei
This paper was aimed to investigate the effect of Aralia echinocaulis containing serum on expression of β-catenin, Wnt-1, Frizzed-2, TCF and Axin in Wnt/β-catenin signaling pathway of primary osteoblasts. SD healthy female rats (n=80) were used to make A. echinocaulis containing serum by gastric perfusion for seven days with distilled water, A. echinocaulis decoction high dosage, middle dosage, and low dosage. In vitro, primary osteoblasts were cultured and identified. The third generation primary osteoblasts were taken and cultured for 48 h, then cells were treated with the different drug serums for 10 days and calcified nodules were counted by alizarin red staining...
July 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29055830/pharmacological-inhibition-of-tankyrase-induces-bone-loss-in-mice-by-increasing-osteoclastogenesis
#3
Shunichi Fujita, Tomoyuki Mukai, Takafumi Mito, Shoko Kodama, Akiko Nagasu, Mizuho Kittaka, Teruki Sone, Yasuyoshi Ueki, Yoshitaka Morita
Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and degradation of target proteins. Since tankyrase inhibitors suppress the degradation of AXIN protein, a negative regulator of the canonical Wnt pathway, they effectively act as Wnt inhibitors. Small molecule tankyrase inhibitors are being investigated as drug candidates for cancer and fibrotic diseases, in which the Wnt pathways are aberrantly activated. Tankyrase is also reported to degrade the adaptor protein SH3BP2 (SH3 domain-binding protein 2)...
October 18, 2017: Bone
https://www.readbyqxmd.com/read/29039516/baicalin-alleviates-h2o2%C3%A2-induced-injury-of-h9c2-cardiomyocytes-through-suppression-of-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway
#4
Liman Qiu, Jinxiao Chen, Jing Lin, Da Wo, Jianfeng Chu, Jun Peng
Baicalin is one of the active ingredients extracted from the dry root of Scutellaria baicalensis Georgi, which has been reported to be effective in preventing myocardial ischemia reperfusion injury. However, the mechanisms underlying its cardioprotective activities remain to be elucidated. In the present study, H2O2‑treated cardiomyocyte H9c2 cell line served as an in vitro model of oxidation‑damaged cardiomyocytes to evaluate the effects of baicalin on the cardiac injury, and to investigate the underlying molecular mechanism...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29034085/amp-activated-protein-kinase-not-just-an-energy-sensor
#5
REVIEW
David Grahame Hardie, Sheng-Cai Lin
Orthologues of AMP-activated protein kinase (AMPK) occur in essentially all eukaryotes as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits. The canonical role of AMPK is as an energy sensor, monitoring levels of the nucleotides AMP, ADP, and ATP that bind competitively to the γ subunit. Once activated, AMPK acts to restore energy homeostasis by switching on alternate ATP-generating catabolic pathways while switching off ATP-consuming anabolic pathways. However, its ancestral role in unicellular eukaryotes may have been in sensing of glucose rather than energy...
2017: F1000Research
https://www.readbyqxmd.com/read/29028954/1-benzyl-indole-3-carbinol-is-a-highly-potent-new-small-molecule-inhibitor-of-wnt-%C3%AE-catenin-signaling-in-melanoma-cells-that-coordinately-inhibits-cell-proliferation-and-disrupts-expression-of-microphthalmia-associated-transcription-factor-isoform-m
#6
Aishwarya Kundu, Michelle G Khouri, Sheila Aryana, Gary L Firestone
1-Benzyl-indole-3-carbinol (1-benzyl-I3C), a synthetic analogue of the crucifer derived natural phytochemical I3C, displayed significantly wider sensitivity and anti-proliferative potency in melanoma cells than the natural compound. Unlike I3C, which targets mainly oncogenic BRAF-expressing cells, 1-benzyl I3C effectively inhibited proliferation of melanoma cells with a more extensive range of mutational profiles, including those expressing wild type BRAF. In both cultured melanoma cell lines and in vivo in melanoma cell-derived tumor xenografts, 1-benzyl-I3C disrupted canonical Wnt/β-catenin signaling that resulted in the down regulation of β-catenin protein levels with a concomitant increase in levels of the β-catenin destruction complex components GSK3β and Axin...
September 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29027899/metformin-extends-c-elegans-lifespan-through-lysosomal-pathway
#7
Jie Chen, Yuhui Ou, Yi Li, Shumei Hu, Li-Wa Shao, Ying Liu
Metformin, a widely used first-line drug for treatment of type 2 diabetes (T2D), has been shown to extend lifespan and delay the onset of age-related diseases. However, its primary locus of action remains unclear. Using a pure in vitro reconstitution system, we demonstrate that metformin acts through the v-ATPase-Ragulator lysosomal pathway to coordinate mTORC1 and AMPK, two hubs governing metabolic programs. We further show in Caenorhabditis elegans that both v-ATPase-mediated TORC1 inhibition and v-ATPase-AXIN/LKB1-mediated AMPK activation contribute to the lifespan extension effect of metformin...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/28970068/skl2001-suppresses-colon-cancer-spheroid-growth-through-regulation-of-the-e-cadherin-%C3%AE-catenin-complex
#8
Wakana Ohashi, Naoki Yamamine, Johji Imura, Yuichi Hattori
Aberrant activation of Wnt signaling plays a pivotal role in the development of human cancers including colon cancer. Small compounds that regulate Wnt signaling are attractive candidate for the colon cancer therapy. Here, we showed that SKL2001, which has been identified as an activator for Wnt signaling by disrupting the Axin/β-Catenin complex, negatively regulates growth of colon cancer spheroids cultured in the 3D condition that simulates tumor microenvironment in vivo. SKL2001 inhibited proliferation of colon cancer cells cultured in 3D spheroid and induced them accumulation in the G0/G1 phase of the cell cycle with a reduced c-myc level...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28968956/thyroid-cancer-1-c8orf4-shows-high-expression-no-mutation-and-reduced-methylation-level-in-lung-cancers-and-its-expression-correlates-with-%C3%AE-catenin-and-dnmt1-expression-and-poor-prognosis
#9
Yi-Wen Zheng, Li Zhang, Yuan Wang, Song-Yan Chen, Lei Lei, Na Tang, Da-Lei Yang, Lin-Lin Bai, Xiu-Peng Zhang, Gui-Yang Jiang, Lian-He Yang, Hong-Tao Xu, Qing-Chang Li, Xue-Shan Qiu, En-Hua Wang
Thyroid cancer 1 (TC1, C8orf4) plays important roles in tumors. The aim of this study was to examine the protein expression levels, methylation status, and mutational status of TC1 (C8orf4) in lung cancers, and investigate the correlation between TC1, other members of the Wnt signaling pathway, and lung cancer. TC1 expression levels were assessed via immunohistochemical staining in 179 cases of lung cancer. β-catenin, TCF4, Axin, Disabled-2, Chibby, and DNA methyltransferase-1 (DNMT1) expressions were also examined...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28941231/assembly-and-architecture-of-the-wnt-%C3%AE-catenin-signalosome-at-the-membrane
#10
REVIEW
Zachary J DeBruine, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is initiated by a ternary Wnt-Frizzled-LRP5/6 binding event. The resulting conformational changes in the Frizzled (FZD) and LRP5/6 receptors promote assembly of an intracellular signalosome driven by Dishevelled and Axin co-polymerization. Recent evidence suggests that FZD and LRP5/6 participate in assembly of this signalosome by forming regulatory scaffolds for stabilizing Dishevelled and Axin adapters. In this review, we focus on the contributions of Wnts and their receptors in assembly of the signalosome...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28895414/knockdown-of-tripartite-motif-containing-28-suppresses-the-migration-invasion-and-epithelial-mesenchymal-transition-in-ovarian-carcinoma-cells-through-down-regulation-of-wnt-%C3%AE-catenin-signaling-pathway
#11
B Deng, S Zhang, Y Zhang, Y Miao, X Meng, K Guo
Tripartite motif containing 28 (TRIM28) is a transcriptional corepressor of Kruppel-associated box zinc finger protein, which has been reported to participate in carcinogenesis. Nonetheless, whether TRIM28 plays a role in the metastasis of ovarian carcinoma (OC) is unclear and requires further investigation. In this study, two OC cell lines (A2780 and OVCAR-3) with stable low expression of TRIM28 were established via RNA interference. We found that the migratory and invasive ability of TRIM28-silenced OC cells significantly decreased...
September 12, 2017: Neoplasma
https://www.readbyqxmd.com/read/28829046/twa1-gid8-is-a-%C3%AE-catenin-nuclear-retention-factor-in-wnt-signaling-and-colorectal-tumorigenesis
#12
Yi Lu, Shanshan Xie, Wen Zhang, Cheng Zhang, Cheng Gao, Qiang Sun, Yuqi Cai, Zhangqi Xu, Min Xiao, Yanjun Xu, Xiao Huang, Ximei Wu, Wei Liu, Fudi Wang, Yibin Kang, Tianhua Zhou
Hyperactivation of Wnt/β-catenin signaling is one of the major causes of human colorectal cancer (CRC). A hallmark of Wnt signaling is the nuclear accumulation of β-catenin. Although β-catenin nuclear import and export have been widely investigated, the underlying mechanism of β-catenin's nuclear retention remains largely unknown. Here, we report that Twa1/Gid8 is a key nuclear retention factor for β-catenin during Wnt signaling and colorectal carcinogenesis. In the absence of Wnt, Twa1 exists together with β-catenin in the Axin complex and undergoes ubiquitination and degradation...
August 22, 2017: Cell Research
https://www.readbyqxmd.com/read/28827348/reversal-of-hyperactive-wnt-signaling-dependent-adipocyte-defects-by-peptide-boronic-acids
#13
Tianyi Zhang, Fu-Ning Hsu, Xiao-Jun Xie, Xiao Li, Mengmeng Liu, Xinsheng Gao, Xun Pei, Yang Liao, Wei Du, Jun-Yuan Ji
Deregulated Wnt signaling and altered lipid metabolism have been linked to obesity, diabetes, and various cancers, highlighting the importance of identifying inhibitors that can modulate Wnt signaling and aberrant lipid metabolism. We have established a Drosophila model with hyperactivated Wnt signaling caused by partial loss of axin, a key component of the Wnt cascade. The Axin mutant larvae are transparent and have severe adipocyte defects caused by up-regulation of β-catenin transcriptional activities. We demonstrate pharmacologic mitigation of these phenotypes in Axin mutants by identifying bortezomib and additional peptide boronic acids...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28810742/determination-of-rate-limiting-factor-for-formation-of-beta-catenin-destruction-complexes-using-absolute-protein-quantification
#14
Masashi Kitazawa, Tomohisa Hatta, Koji Ogawa, Eriko Fukuda, Naoki Goshima, Tohru Natsume
Wnt/β-catenin signaling plays important roles in both ontogenesis and development. In the absence of a Wnt stimulus, β-catenin is degraded by a multiprotein "destruction complex" that includes Axin, APC, GSK3B, and FBXW11. Although the key molecules required for transducing Wnt signals have been identified, a quantitative understanding of this pathway has been lacking. Here, we calculated the absolute number of β-catenin destruction complexes by absolute protein quantification using LC-MS/MS. Similar amounts of destruction complex-constituting proteins and β-catenin interacted, and the number of destruction complexes was calculated to be about 1468 molecules/cell...
September 1, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28800791/microrna-154-inhibits-the-growth-and-invasion-of-gastric-cancer-cells-by-targeting-dixdc1-wnt-signaling
#15
Jifu Song, Zhibin Guan, Maojiang Li, Sha Sha, Chao Song, Zhiwei Gao, Yongli Zhao
MicroRNAs (miRNAs) have emerged as pivotal regulators of the development and progression of gastric cancer. Studies have shown that miR-154 is a novel cancer-associated miRNA involved in various cancers. However, the role of miR-154 in gastric cancer remains unknown. Here we aimed to investigate the biological function and the potential molecular mechanism of miR-154 in gastric cancer. We found that miR-154 was significantly downregulated in gastric cancer tissues and cell lines. The overexpression of miR-154 significantly repressed the growth and invasion of gastric cancer cells...
August 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28798413/structural-basis-for-ccd1-auto-inhibition-in-the-wnt-pathway-through-homomerization-of-the-dix-domain
#16
Shin-Ichi Terawaki, Shohei Fujita, Takuya Katsutani, Kensuke Shiomi, Kazuko Keino-Masu, Masayuki Masu, Kaori Wakamatsu, Naoki Shibata, Yoshiki Higuchi
Wnt signaling plays an important role in governing cell fate decisions. Coiled-coil-DIX1 (Ccd1), Dishevelled (Dvl), and Axin are signaling proteins that regulate the canonical pathway by controlling the stability of a key signal transducer β-catenin. These proteins contain the DIX domain with a ubiquitin-like fold, which mediates their interaction in the β-catenin destruction complex through dynamic head-to-tail polymerization. Despite high sequence similarities, mammalian Ccd1 shows weaker stimulation of β-catenin transcriptional activity compared with zebrafish (z) Ccd1 in cultured cells...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794794/sfrp2-enhances-the-osteogenic-differentiation-of-apical-papilla-stem-cells-by-antagonizing-the-canonical-wnt-pathway
#17
Luyuan Jin, Yu Cao, Guoxia Yu, Jinsong Wang, Xiao Lin, Lihua Ge, Juan Du, Liping Wang, Shu Diao, Xiaomeng Lian, Songlin Wang, Rui Dong, Zhaochen Shan
BACKGROUND: Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor, could enhance osteogenic differentiation in stem cells from the apical papilla (SCAPs). However, how SFRP2 promotes osteogenic differentiation of dental tissue-derived MSCs remains unclear...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28772205/anti-proliferative-activity-of-cgk012-against-multiple-myeloma-cells-via-wnt-%C3%AE-catenin-signaling-attenuation
#18
Pyung Jun Choi, Yuseok O, Jin-Hyuk Her, Eunju Yun, Gyu Yong Song, Sangtaek Oh
The aberrant activation of Wnt/β-catenin signaling is involved in the development of multiple myeloma; thus, this signaling pathway is a potential target for the development of therapeutics for this malignancy. Here, we performed cell-based chemical screening and found that CGK012, a pyranocoumarin compound, suppressed the Wnt3a-CM-mediated activation of β-catenin response transcription. CGK012 induced β-catenin phosphorylation at Ser33/Ser37/Thr41, leading to proteasomal degradation and reducing the level of intracellular β-catenin...
September 2017: Leukemia Research
https://www.readbyqxmd.com/read/28770488/identification-and-characterization-of-functional-single-nucleotide-polymorphisms-snps-in-axin-1-gene-a-molecular-dynamics-approach
#19
Imran Khan, Irfan A Ansari, Pratichi Singh, J Febin Prabhu Dass, Fahad Khan
Wnt signaling pathway has been reported to play crucial role in intestinal crypt formation and deregulation of this pathway is responsible for colorectal cancer initiation and progression. Axin 1, a scaffold protein, play pivotal role in the regulation of Wnt/β-catenin signaling pathway and has been found to be mutated in several cancers; primarily in colon cancer. Considering its crucial role, a structural and functional analysis of missense mutations in Axin 1 gene was performed in this study. Initially, one hundred non-synonymous single nucleotide polymorphisms in the coding regions of Axin 1 gene were selected for in silico analysis...
August 2, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28741966/the-connections-of-wnt-pathway-components-with-cell-cycle-and-centrosome-side-effects-or-a-hidden-logic
#20
Vítězslav Bryja, Igor Červenka, Lukáš Čajánek
Wnt signaling cascade has developed together with multicellularity to orchestrate the development and homeostasis of complex structures. Wnt pathway components - such as β-catenin, Dishevelled (DVL), Lrp6, and Axin-- are often dedicated proteins that emerged in evolution together with the Wnt signaling cascade and are believed to function primarily in the Wnt cascade. It is interesting to see that in recent literature many of these proteins are connected with cellular functions that are more ancient and not limited to multicellular organisms - such as cell cycle regulation, centrosome biology, or cell division...
July 25, 2017: Critical Reviews in Biochemistry and Molecular Biology
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