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https://www.readbyqxmd.com/read/29158412/induced-gnas-r201h-expression-from-the-endogenous-gnas-locus-causes-fibrous-dysplasia-by-up-regulating-wnt-%C3%AE-catenin-signaling
#1
Sanjoy Kumar Khan, Prem Swaroop Yadav, Gene Elliott, Dorothy Zhang Hu, Ruoshi Xu, Yingzi Yang
Fibrous dysplasia (FD; Online Mendelian Inheritance in Man no. 174800) is a crippling skeletal disease caused by activating mutations of the GNAS gene, which encodes the stimulatory G protein Gαs FD can lead to severe adverse conditions such as bone deformity, fracture, and severe pain, leading to functional impairment and wheelchair confinement. So far there is no cure, as the underlying molecular and cellular mechanisms remain largely unknown and the lack of appropriate animal models has severely hampered FD research...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29135090/gene-expression-profiling-demonstrates-wnt-%C3%AE-catenin-pathway-genes-alteration-in-mexican-patients-with-colorectal-cancer-and-diabetes-mellitus
#2
Laura Ivonne Wence-Chavez, Ulises Palomares-Chacon, Juan Pablo Flores-Gutierrez, Luis Felipe Jave-Suarez, Adriana Del Carmen Aguilar-Lemarroy, Patricio Barros-Nunez, Silvia Esperanza Flores-Martinez, Jose Sanchez-Corona, Monica Alejandra Rosales-Reynoso
PURPOSE: Several studies have shown a strong association between diabetes mellitus (DM) and increased risk of colorectal cancer (CRC). The fundamental mechanisms that support this association are not entirely understood; however, it is believed that hyperinsulinemia and hyperglycemia may be involved. Some proposed mechanisms include upregulation of mitogenic signaling pathways like MAPK, PI3K, mTOR, and WNT, which are involved in cell proliferation, growth, and cancer cell survival. The purpose of this study was to evaluate the gene expression profile and identify differently expressed genes involved in mitogenic pathways in CRC patients with and without DM...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29131552/activation-of-the-wnt-pathway-by-small-peptides-rational-design-synthesis-and-biological-evaluation
#3
Simone Brogi, Samuele Maramai, Margherita Brindisi, Giulia Chemi, Valentina Porcari, Claudio Corallo, Luigi Gennari, Ettore Novellino, Anna Ramunno, Stefania Butini, Giuseppe Campiani, Sandra Gemma
A computational analysis of the X-ray structure of the low-density lipoprotein receptor-related protein 6 (LRP6) with Dickkopf-1 (DKK1) C-terminal fragment has allowed us to rationally design a small set of decapeptides (1a-e). These compounds behave as agonists of the canonical Wnt pathway in the micromolar range when tested on a dual luciferase Wnt functional assay in glioblastoma cells. Lack of cellular toxicity was assessed for compounds 1c and 1d in human primary osteoblasts isolated from sponge bone tissue (femoral heads or knee of old patients)...
November 13, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29118355/decoy-wnt-receptor-slrp6e1e2-expressing-adenovirus-induces-anti-fibrotic-effect-via-inhibition-of-wnt-and-tgf-%C3%AE-signaling
#4
Won Jai Lee, Jung-Sun Lee, Hyo Min Ahn, Youjin Na, Chae Eun Yang, Ju Hee Lee, JinWoo Hong, Chae-Ok Yun
Aberrant activation of the canonical Wingless type (Wnt) signaling pathway plays a key role in the development of hypertrophic scars and keloids, and this aberrant activation of Wnt pathway can be a potential target for the development of novel anti-fibrotic agents. In this study, we evaluated the anti-fibrotic potential of a soluble Wnt decoy receptor (sLRP6E1E2)-expressing non-replicating adenovirus (Ad; dE1-k35/sLRP6E1E2) on human dermal fibroblasts (HDFs), keloid fibroblasts (KFs), and keloid tissue explants...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29098038/exogenous-dkk-3-reic-inhibits-wnt-%C3%AE-catenin-signaling-and-cell-proliferation-in-human-kidney-cancer-kpk1
#5
Jiaqi Xu, Takuya Sadahira, Rie Kinoshita, Shun-Ai Li, Peng Huang, Koichiro Wada, Motoo Araki, Kazuhiko Ochiai, Hirofumi Noguchi, Masakiyo Sakaguchi, Yasutomo Nasu, Masami Watanabe
The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/β-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29091885/lipid-rafts-disruption-induces-apoptosis-by-attenuating-expression-of-lrp6-and-survivin-in-triple-negative-breast-cancer
#6
Anil Kumar Badana, Madhuri Chintala, Murali Mohan Gavara, Shailender Naik, Seema Kumari, Vijaya Rachel Kappala, Bhaskar Reddy Iska, Rama Rao Malla
Triple negative breast cancer is a clinically challenging subtype due to lack of biomarker for rational targeted therapy. Lipid rafts are cholesterol enriched rigid platforms, which colocalize signalling molecules of cancer progression. This study explores the effect of lipid rafts disruption by cholesterol depleting agent, MβCD on induction of apoptosis and expression of WNT receptor LRP6, survivin and common apoptotic markers in TNBC cell lines. The in vitro effect of lipid rafts disruption on viability, single cell reproductive ability, proliferation and migration were evaluated by MTT, clonogenic, BrdU incorporation and wound scratch assays, respectively...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29038835/interaction-between-lrp5-and-periostin-gene-polymorphisms-on-serum-periostin-levels-and-cortical-bone-microstructure
#7
J Pepe, N Bonnet, F R Herrmann, E Biver, R Rizzoli, T Chevalley, S L Ferrari
We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. PURPOSE: The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women...
October 16, 2017: Osteoporosis International
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
#8
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/29017031/angiopoietin-like-4-is-a-wnt-signaling-antagonist-that-promotes-lrp6-turnover
#9
Nadine Kirsch, Ling-Shih Chang, Stefan Koch, Andrey Glinka, Christine Dolde, Gabriele Colozza, Maria D J Benitez, Edward M De Robertis, Christof Niehrs
Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6). This protein complex is internalized via clathrin-mediated endocytosis and degraded in lysosomes, leading to attenuation of Wnt/β-catenin signaling...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28982588/low-1-level-mechanical-vibration-improves-bone-microstructure-tissue-mechanical-properties-and-porous-titanium-implant-osseointegration-by-promoting-anabolic-response-in-type-1-diabetic-rabbits
#10
Da Jing, Zedong Yan, Jing Cai, Shichao Tong, Xiaokang Li, Zheng Guo, Erping Luo
Type 1 diabetes mellitus (T1DM) is associated with reduced bone mass, increased fracture risk, and impaired bone defect regeneration potential. These skeletal complications are becoming important clinical challenges due to the rapidly increasing T1DM population, which necessitates developing effective treatment for T1DM-associated osteopenia/osteoporosis and bone trauma. This study aims to investigate the effects of whole-body vibration (WBV), an easy and non-invasive biophysical method, on bone microstructure, tissue-level mechanical properties and porous titanium (pTi) osseointegration in alloxan-diabetic rabbits...
October 2, 2017: Bone
https://www.readbyqxmd.com/read/28981473/novel-eda-or-edar-mutations-identified-in-patients-with-x-linked-hypohidrotic-ectodermal-dysplasia-or-non-syndromic-tooth-agenesis
#11
Binghui Zeng, Qi Zhao, Sijie Li, Hui Lu, Jiaxuan Lu, Lan Ma, Wei Zhao, Dongsheng Yu
Abstract: Both X-linked hypohidrotic ectodermal dysplasia (XLHED) and non-syndromic tooth agenesis (NSTA) result in symptoms of congenital tooth loss. This study investigated genetic causes in two families with XLHED and four families with NSTA. We screened for mutations of WNT10A, EDA, EDAR, EDARADD, PAX9, MSX1, AXIN2, LRP6, and WNT10B through Sanger sequencing. Whole exome sequencing was performed for the proband of NSTA Family 4. Novel mutation c.1051G>T (p.Val351Phe) and the known mutation c.467G>A (p...
October 5, 2017: Genes
https://www.readbyqxmd.com/read/28980049/effects-of-endogenous-hypercortisolism-on-bone-mrna-and-microrna-expression-in-humans
#12
Z E Belaya, T A Grebennikova, G A Melnichenko, A G Nikitin, A G Solodovnikov, O I Brovkina, A U Grigoriev, L Y Rozhinskaya, I I Dedov
Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts. INTRODUCTION: The purpose of this study was to evaluate the responses of bone to chronic glucocorticoid (GC) excess by measuring the levels of selected mRNA and microRNA (miR) in bone samples of patients with Cushing's disease (CD)...
October 4, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28966723/extracellular-ldlr-repeats-modulate-wnt-signaling-activity-by-promoting-lrp6-receptor-endocytosis-mediated-by-the-itch-e3-ubiquitin-ligase
#13
Sapna Vijayakumar, Guizhong Liu, Huei-Chi Wen, Yaa Abu, Robert Chong, Horacio Nastri, Gadi G Bornstein, Zhen-Qiang Pan, Stuart A Aaronson
The LOW-density lipoprotein related protein 6 (LRP6) receptor is an important effector of canonical Wnt signaling, a developmental pathway, whose dysregulation has been implicated in various diseases including cancer. The membrane proximal low-density lipoprotein (LDL) receptor repeats in LRP6 exhibit homology to ligand binding repeats in the LDL receptor (LDLR), but lack known function. We generated single amino acid substitutions of LRP6-LDLR repeat residues, which are highly conserved in the human LDLR and mutated in patients with Familial Hypercholesteremia (FH)...
July 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28960852/novel-mutation-of-lrp6-identified-in-chinese-han-population-links-canonical-wnt-signaling-to-neural-tube-defects
#14
Zhiwen Shi, Xueyan Yang, Bin-Bin Li, Shuxia Chen, Luming Yang, Liangping Cheng, Ting Zhang, Hongyan Wang, Yufang Zheng
BACKGROUND: Neural tube defects (NTDs), the second most frequent cause of human congenital abnormalities, are debilitating birth defects due to failure of neural tube closure. It has been shown that noncanonical WNT/planar cell polarity (PCP) signaling is required for convergent extension (CE), the initiation step of neural tube closure (NTC). But the effect of canonical WNT//β-catenin signaling during NTC is still elusive. LRP6 (low density lipoprotein receptor related proteins 6) was identified as a co-receptor for WNT/β-catenin signaling, but recent studies showed that it also can mediate WNT/PCP signaling...
September 29, 2017: Birth defects research
https://www.readbyqxmd.com/read/28919327/endothelial-microparticle-promoted-inhibition-of-vascular-remodeling-is-abrogated-under-hyperglycaemic-conditions
#15
Felix Jansen, Andreas Zietzer, Tobias Stumpf, Anna Flender, Theresa Schmitz, Georg Nickenig, Nikos Werner
BACKGROUND: Endothelial microparticles (EMPs) inhibit vascular remodeling by transferring functional microRNA (miRNA) into target vascular smooth muscle cells (VSMCs). Because EMPs are increased in diabetic patients and potentially linked to vascular complications in diabetes mellitus, we sought to determine whether effects of EMPs generated under high glucose concentration on vascular remodeling might differ from EMPs derived from untreated cells. METHODS AND RESULTS: EMPs were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions...
September 14, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28880263/lrp6-is-identified-as-a-potential-prognostic-marker-for-oral-squamous-cell-carcinoma-via-maldi-ims
#16
Yao Yuan, Xiaoyan Xie, Yuchen Jiang, Zihao Wei, Peiqi Wang, Fangman Chen, Xinyi Li, Chongkui Sun, Hang Zhao, Xin Zeng, Lu Jiang, Yu Zhou, Hongxia Dan, Mingye Feng, Rui Liu, Zhiyong Wang, Qianming Chen
Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, with 500 000 new cases each year. However, the mechanisms underlying OSCC development are relatively unknown. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was used to profile the differentially expressed peptides/proteins between OSCC tissues and their adjacent noncancerous tissues. Sixty-seven unique peptide peaks and five distinct proteins were identified with changed expression levels...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28870205/maintenance-of-stemness-is-associated-with-the-interation-of-lrp6-and-heparin-binding-protein-ccn2-autocrined-by-hepatocellular-carcinoma
#17
Qingan Jia, Yang Bu, Zhiming Wang, Bendong Chen, Qiangbo Zhang, Songning Yu, Qingguang Liu
BACKGROUND: The overall response rate of hepatocellular carcinoma (HCC) to chemotherapy is poor. In our previous study, oxaliplatin-resistant HCC is found to exhibit an enhanced stemness, and increased levels of CCN2 and LRP6, while the role of CCN2 and LRP6 in the prognosis of HCC patients, and the interaction regulation mechanism between CCN2 and LRP6 are still unclear. METHODS: The expression levels of CCN2 and LRP6 were detected in large cohorts of HCCs, and functional analyses of CCN2 and LRP6 were performed both in vitro and in vivo...
September 4, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28861168/inhibition-of-wnt-%C3%AE-catenin-by-anthelmintic-drug-niclosamide-effectively-targets-growth-survival-and-angiogenesis-of-retinoblastoma
#18
Zhi Li, Qin Li, Genguo Wang, Yi Huang, Xiaochun Mao, Yanfang Zhang, Xueyan Wang
Retinoblastoma is an angiogenesis-dependent ocular tumor, the clinical management of which remains a challenge. Agents that can target tumor cells and angiogenesis, as well as augment current chemotherapy efficacy, present a promising therapeutic strategy for retinoblastoma. We demonstrated that niclosamide, an FDA-approved anthelmintic drug, is effective against multiple aspects of retinoblastoma. Niclosamide inhibited proliferation via causing cell cycle arrest at the G2/M phase and induced caspase-dependent apoptosis in a panel of retinoblastoma cell lines, including Y79, RB116, and WERI-Rb-1...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28821575/ldl-switches-the-lrp6-internalization-route-from-flotillin-dependent-to-clathrin-dependent-in-hepatic-cells
#19
Hideki Yamamoto, Daisuke Umeda, Shinji Matsumoto, Akira Kikuchi
Low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) was originally identified as a coreceptor of the Wnt signaling pathway and has been shown to be involved in LDL transport. In polarized hepatocytes, many apical proteins are sorted to the basolateral membrane and then internalized and transported to the apical bile canalicular membrane-a process known as transcytosis. Herein, we show that LRP6 is transcytosed to the apical membrane of polarized hepatic HepG2 cells via a flotillin-dependent manner in the absence of LDL...
August 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28815294/diallyl-trisulfide-inhibits-proliferation-invasion-and-angiogenesis-of-glioma-cells-by-inactivating-wnt-%C3%AE-catenin-signaling
#20
Qingxia Tao, Cuiying Wu, Ruxiang Xu, Lijun Niu, Jiazhen Qin, Ning Liu, Peng Zhang, Chong Wang
Aberrant activation of Wnt/β-catenin signaling leads to increased cell proliferation and survival and promotes the development of various human tumors, including glioma, one of the most common primary brain tumors. The treatment efficacy of many anticancer drugs remains limited or unsatisfactory and it is urgently necessary to develop effective and low-toxicity anticancer drugs or strategies, especially for glioma. Here, we report that diallyl trisulfide suppresses survival, migration, invasion and angiogenesis in glioma cells...
August 17, 2017: Cell and Tissue Research
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