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https://www.readbyqxmd.com/read/29340077/lrp6-targeting-suppresses-gastric-tumorigenesis-via-p14arf-mdm2-p53-dependent-cellular-senescence
#1
Haibin Wang, Guoxing Xu, Zhengjie Huang, Weizheng Li, Huali Cai, Yunda Zhang, Disheng Xiong, Gang Liu, Shengjie Wang, Zengfu Xue, Qi Luo
NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29335534/cell-type-specific-potent-wnt-signaling-blockade-by-bispecific-antibody
#2
Nam-Kyung Lee, Yafeng Zhang, Yang Su, Scott Bidlingmaier, Daniel W Sherbenou, Kevin D Ha, Bin Liu
Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29312635/lrp6-promotes-invasion-and-metastasis-of-colorectal-cancer-through-cytoskeleton-dynamics
#3
Qian Yao, Yu An, Wei Hou, Ya-Nan Cao, Meng-Fei Yao, Ning-Ning Ma, Lin Hou, Hong Zhang, Hai-Jing Liu, Bo Zhang
Low density lipoprotein (LDL) receptor-related protein-6 (LRP6) is an important co-receptor of Wnt pathway, which plays a predominant role in development and progression of colorectal cancer. Recently, dysregulation of LRP6 has proved to be involved in the progression of cancers, but its biological role and clinical significance in colorectal cancer remain unclear. In present study, we revealed that phosphorylation of LRP6 was aberrantly upregulated in colorectal carcinoma correlating with TNM or Dukes staging and worse prognosis...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29259894/suppression-of-corneal-neovascularization-by-curcumin-via-inhibition-of-wnt-%C3%AE-catenin-pathway-activation
#4
Yong-Kang Zhang, Jing-Ming Li, Li Qin
AIM: To investigate whether curcumin suppressed corneal neovascularization (CNV) formation via inhibiting activation of Wnt/β-catenin pathway. METHODS: Suture-induced CNV was established on Sprague-Dawley (SD) rats. Curcumin were daily administrated by subconjunctival injection. Phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6) and nuclear accumulation of β-catenin, two indicators of activated Wnt/β-catenin pathway, were determined by Western-blot analysis in subconfluent/proliferating human microvascular endothelial cells (HMEC) and neovascularized corneas...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29243438/-effects-of-aqueous-extracts-of-gecko-on-stemness-of-hepatocellular-carcinoma
#5
Hui-Ling Huang, Ya-Lan Zhang, Wen-Fa Chen, Chun-Ling Wu
To explore the effects and mechanism of aqueous extracts of gecko on cancer stem cells properties of hepatocellular carcinoma. In vitro, MTT assay was used to detect the cells growth in Huh7 and Hep3B. Spheroid-forming assay and flow cytometry were performed to observe the the stemness of Huh7 and Hep3B cells. The protein expressions of β-catenin, CD44, c-Myc, CCND1, Sox2, Oct4, Nanog and ABCG2 were detected by Western blot. Interacting proteins were detected by co-immunoprecipitation; and a subcutaneous xenograft model was used to detect the stemness of hepatoma carcinoma cells...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29243194/kallistatin-inhibits-lymphangiogenesis-and-lymphatic-metastasis-of-gastric-cancer-by-downregulating-vegf-c-expression-and-secretion
#6
Caiqi Ma, Chuanghua Luo, Haofan Yin, Yang Zhang, Wenjun Xiong, Ting Zhang, Tianxiao Gao, Xi Wang, Di Che, Zhenzhen Fang, Lei Li, Jinye Xie, Mao Huang, Liuqing Zhu, Ping Jiang, Weiwei Qi, Ti Zhou, Zhonghan Yang, Wei Wang, Jianxing Ma, Guoquan Gao, Xia Yang
BACKGROUND: Tumor-induced lymphangiogenesis and lymphatic metastasis are predominant during the metastasis of many types of cancers. However, the endogenous inhibitors that counterbalance the lymphangiogenesis and lymphatic metastasis of tumors have not been well evaluated. Kallistatin has been recognized as an endogenous angiogenesis inhibitor. METHODS AND RESULTS: Our recent study showed for the first time that the lymphatic vessel density (LVD) was reduced in lung and stomach sections from kallistatin-overexpressing transgenic mice...
December 14, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/29228616/microrna-610-inhibits-tumor-growth-of-melanoma-by-targeting-lrp6
#7
Guangjing Zhang, Dongfang Ai, Xiufang Yang, Shanshan Ji, Zhengxiang Wang, Shijun Feng
Accumulating evidence showed that aberrant miRNAs expression was involved in initiation and progression of melanoma. However, the investigation of different miRNAs in melanoma remain attractive. In this research, we demonstrated that miR-610 expression was decreased in melanoma tissues and cell lines. The clinical data showed that the reduced miR-610 expression was obviously associated with adverse prognostic characteristics. Furthermore, our results suggested that miR-610 had a function of prognostic indicator for 5-year predicted-survival of melanoma patients...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215008/roles-of-two-types-of-heparan-sulfate-clusters-in-wnt-distribution-and-signaling-in-xenopus
#8
Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, Shinji Takada, Masanori Taira
Wnt proteins direct embryonic patterning, but the regulatory basis of their distribution and signal reception remain unclear. Here, we show that endogenous Wnt8 protein is distributed in a graded manner in Xenopus embryo and accumulated on the cell surface in a punctate manner in association with "N-sulfo-rich heparan sulfate (HS)," not with "N-acetyl-rich HS". These two types of HS are differentially clustered by attaching to different glypicans as core proteins. N-sulfo-rich HS is frequently internalized and associated with the signaling vesicle, known as the Frizzled/Wnt/LRP6 signalosome, in the presence of Wnt8...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29176883/wnt-co-receptors-lrp5-and-lrp6-differentially-mediate-wnt3a-signaling-in-osteoblasts
#9
Aimy Sebastian, Nicholas R Hum, Deepa K Murugesh, Sarah Hatsell, Aris N Economides, Gabriela G Loots
Wnt3a is a major regulator of bone metabolism however, very few of its target genes are known in bone. Wnt3a preferentially signals through transmembrane receptors Frizzled and co-receptors Lrp5/6 to activate the canonical signaling pathway. Previous studies have shown that the canonical Wnt co-receptors Lrp5 and Lrp6 also play an essential role in normal postnatal bone homeostasis, yet, very little is known about specific contributions by these co-receptors in Wnt3a-dependent signaling. We used high-throughput sequencing technology to identify target genes regulated by Wnt3a in osteoblasts and to elucidate the role of Lrp5 and Lrp6 in mediating Wnt3a signaling...
2017: PloS One
https://www.readbyqxmd.com/read/29158412/induced-gnasr201h-expression-from-the-endogenous-gnas-locus-causes-fibrous-dysplasia-by-up-regulating-wnt-%C3%AE-catenin-signaling
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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