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https://www.readbyqxmd.com/read/30098400/tannins-from-syzygium-guineense-suppress-wnt-signaling-and-proliferation-of-wnt-dependent-tumors-through-a-direct-effect-on-secreted-wnts
#1
Alexey Koval, Constant A Pieme, Emerson Ferreira Queiroz, Simone Ragusa, Kamal Ahmed, Artem Blagodatski, Jean-Luc Wolfender, Tatiana V Petrova, Vladimir L Katanaev
Triple-negative breast cancer (TNBC) and colon cancer (CC) are two stigmatic examples of poorly treatable tumors, whose progression critically depends upon hyperactivation of the Wnt signaling. Development of specific anti-Wnt inhibitors is required to develop drugs against these and other Wnt-dependent cancers. Natural products, especially plants, have been used for the treatment of various diseases from ancient times. We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells...
August 8, 2018: Cancer Letters
https://www.readbyqxmd.com/read/30096373/a-novel-recombinant-human-frizzled-7-protein-exhibits-anti-tumor-activity-against-triple-negative-breast-cancer-via-abating-wnt-%C3%AE-catenin-pathway
#2
Wei Xie, Yan Zhang, Yuan He, Kunchi Zhang, Guoqing Wan, Yanjuan Huang, Zhaoli Zhou, Gang Huang, Jin Wang
Triple negative breast cancer (TNBC) is one of the most difficult malignancy to treat due to a lack of targeted therapy. Studies have demonstrated that the activation of Wnt/β-catenin signaling was preferentially found in TNBC. Frizzled-7 (Fzd7), one of the Wnt receptors, was significantly up-regulated in TNBC and modulated TNBC tumorigenesis through the Wnt signaling pathway, indicating Fzd7 is a biomarker and a potential therapeutic target for TNBC. Here, we designed a recombinant soluble peptide fragment (rhFzd7) to antagonize Fzd7 by competitively binding with Wnt ligands...
August 7, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/30089773/lgr5-regulates-gastric-adenocarcinoma-cell-proliferation-and-invasion-via-activating-wnt-signaling-pathway
#3
Xiangfei Wang, Xiumin Wang, Yang Liu, Yating Dong, Yanan Wang, Muzaffer Ahmad Kassab, Wufang Fan, Xiaochun Yu, Chen Wu
LGR5 plays a critical role in tissue development and the maintenance of adult stem cells in gastrointestinal tract. However, the oncogenic role of LGR5 in the development of gastric adenocarcinoma remains elusive. Here, we show that LGR5 promotes gastric adenocarcinoma cell proliferation and metastasis. We find that knock down of LGR5 or suppression of Wnt signaling pathway by inhibitor C59 arrests gastric adenocarcinoma cell proliferation and invasion. Moreover, treatment of Wnt3a, the activator of Wnt signaling pathway, partially recovers the proliferation defect observed in LGR5 knockdown gastric adenocarcinoma cells...
August 9, 2018: Oncogenesis
https://www.readbyqxmd.com/read/30072583/mir-155-is-down-regulated-in-familial-adenomatous-polyposis-and-modulates-wnt-signaling-by-targeting-axin1-and-tcf4
#4
Anna Prossomariti, Giulia Piazzi, Leonarda D'Angelo, Sara Miccoli, Daniela Turchetti, Chiara Alquati, Claudio Montagna, Franco Bazzoli, Luigi Ricciardiello
Adenomatous polyposis coli (APC) gene mutations are responsible for the onset of Familial Adenomatous Polyposis (FAP) and sporadic colorectal cancer (CRC) and have been associated with microRNA (miRNA) dysregulation. The capacity of miR-155, a cancer-related miRNA, to target components of the Wnt/β-catenin pathway suggests that APC gene mutations, controlling miRNA expression, may critically regulate Wnt/β-catenin signaling. To this end, APC gene target sequencing was performed on colonic adenomatous polyps and paired normal mucosa clinical specimens from FAP patients (n=9) to elucidate the role of miR-155-5p in APC-mutant setting...
August 2, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/30057241/functional-characterization-of-a-novel-progranulin-mutation-in-a-patient-with-progressive-nonfluent-aphasia
#5
Katarzyna Gaweda-Walerych, Emilia J Sitek, Ewa Narożańska, Michalina Wezyk, Bogna Brockhuis, Cezary Zekanowski, Jarosław Sławek
Loss-of-function mutations in progranulin (PGRN) gene cause frontotemporal lobar degeneration. Here, we report a case of a 63-year-old woman with a 2-year history of speech impairment, diagnosed with a nonfluent variant of primary progressive aphasia, a subtype of frontotemporal lobar degeneration. In this patient, a novel heterozygous frameshift mutation, c.77delG, in exon 2 of PGRN gene, introducing premature stop codon, p.(C26SfsX28), has been identified. Cultured fibroblasts derived from the patient and her asymptomatic first-degree relative with c...
July 2, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/30053090/mir-221-222-activate-the-wnt-%C3%AE-catenin-signaling-to-promote-triple-negative-breast-cancer
#6
Sanhong Liu, Zifeng Wang, Zukai Liu, Shuo Shi, Zhaoran Zhang, Jiawei Zhang, Haifan Lin
Triple-negative breast cancer (TNBC), characterized by the lack of expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, is an aggressive form of cancer that conveys unpredictable and poor prognosis due to limited treatment options and lack of effective targeted therapies. Wnt/β-catenin signaling is hyperactivated in TNBC, which promotes the progression of TNBC. However, the molecular mechanism of Wnt/β-catenin activation in TNBC remains unknown...
July 25, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/30046241/study-of-the-mechanism-of-environmentally-friendly-translucent-balsa-modified-lysozyme-dressing-for-facilitating-wound-healing
#7
Daijun Zhou, Tao Yang, Wei Qian, Malcolm Xing, Gaoxing Luo
Objective: This study aimed to prepare an eco-friendly dressing using a balsa-derived membrane with lysozymes designed for antibacterial purposes. Methods: The groups included controls, balsa (group A), translucent balsa (group B), translucent balsa-lysozymes (group C), and translucent balsa-modified lysozymes (group D). Physical and chemical methods were used to characterize the materials, and the function of the materials was evaluated by in vivo and in vitro experiments...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30035326/impact-of-wnt-signals-on-human-intervertebral-disc-cell-regeneration
#8
Tyler Pizzute, Fan He, Xiao-Bing Zhang, Ming Pei
Although preconditioning strategies are growing areas of interest for therapies targeting intervertebral discs (IVDs), it is unknown whether the Wnt signals previously implicated in chondrogenesis, Wnt3A, Wnt5A, and Wnt11, play key roles in the promotion of human nucleus pulposus (NP) cell redifferentiation. In this study, NP cells isolated from herniated disc patients were transduced with lentiviral vectors to overexpress the WNT3A, WNT5A, or WNT11 genes, or CRISPR associated protein 9 (Cas9)/single-guide RNA (sgRNA) vectors to knock out these genes...
July 23, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/30022568/fluid-shear-stress-improves-morphology-cytoskeleton-architecture-viability-and-regulates-cytokine-expression-in-a-time-dependent-manner-in-mlo-y4-cells
#9
Zedong Yan, Pan Wang, Junjie Wu, Xue Feng, Jing Cai, Mingming Zhai, Juan Li, Xiyu Liu, Maogang Jiang, Erping Luo, Da Jing
The effects of load-induced interstitial fluid shear stress (FSS) on instantaneous signaling response of osteocytes (e.g., calcium signaling) have been well documented. FSS can also initiate the release of many important messenger molecules of osteocytes (e.g., ATP and PGE2 ). However, the effects of FSS on cellular function and bone metabolism-modulating cytokine expression of osteocytes have not been fully identified (some inconsistent/conflicting results have been documented). Herein, osteocyte-like MLO-Y4 cells were stimulated with 1 Pa, 2-h FSS, and the effects of FSS on cellular morphology, cytoskeletal microstructure, biological activity, and gene and protein expression of important cytokines were investigated...
July 18, 2018: Cell Biology International
https://www.readbyqxmd.com/read/30018042/wnt3a-neutralization-enhances-t-cell-responses-through-indirect-mechanisms-and-restrains-tumor-growth
#10
Ilenia Pacella, Ilenia Cammarata, Chiara Focaccetti, Stefano Miacci, Alessandro Gulino, Claudio Tripodo, Micol Ravà, Vincenzo Barnaba, Silvia Piconese
The Wnt/β-catenin pathway regulates T-cell functions, including the repression of effector functions to the advantage of memory development via Tcf1. In a companion study, we demonstrate that, in human cancers, Wnt3a/β-catenin signaling maintains tumor-infiltrating T cells in a partially exhausted status. Here, we have investigated the effects of Wnt3a neutralization in vivo in a mouse tumor model. Abundant Wnt3a was released, mostly by stromal cells, in the tumor microenvironment. We tested whether Wnt3a neutralization in vivo could rescue the effector capacity of tumor-infiltrating T cells, by administering an antibody to Wnt3a to tumor-bearing mice...
August 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/30018041/wnt3a-%C3%AE-catenin-signaling-conditions-differentiation-of-partially-exhausted-t-effector-cells-in-human-cancers
#11
Valeria Schinzari, Eleonora Timperi, Giulia Pecora, Francesco Palmucci, Daniela Gallerano, Alessio Grimaldi, Daniela Angela Covino, Nicola Guglielmo, Fabio Melandro, Emy Manzi, Andrea Sagnotta, Francesco Lancellotti, Luca Sacco, Piero Chirletti, Gian Luca Grazi, Massimo Rossi, Vincenzo Barnaba
In this study, we investigated the role of the Wnt/β-catenin signaling pathway in antitumor immune responses. We report that the concentration of secreted Wnt3a was significantly higher in conditioned medium from tumor or nontumor tissues obtained from all hepatocellular carcinoma or colorectal cancer patients tested, than in serum of healthy donors or patients. In addition, both Wnt3a and β-catenin were overexpressed by tumor-infiltrating and nontumor-infiltrating CD4+ or CD8+ T cells. The majority of these T cells expressed a dysfunctional effector memory Eomes+ T-bet- phenotype that we defined as partially exhausted, because they performed effector functions (in terms of interferon-γ and tumor necrosis factor-α production, as well as CD107a mobilization) despite their PD-1 expression...
August 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/30013637/identification-of-potential-target-genes-in-pancreatic-ductal-adenocarcinoma-by-bioinformatics-analysis
#12
Yuchen Tang, Zixiang Zhang, Yaocheng Tang, Xinyu Chen, Jian Zhou
Pancreatic ductal adenocarcinoma (PDAC) is one of the most complicated and fatally pathogenic human malignancies. Therefore, there is an urgent need to improve our understanding of the underlying molecular mechanism that drives the initiation, progression, and metastasis of PDAC. The aim of the present study was to identify the key genes and signaling pathways associated with PDAC using bioinformatics analysis. Four transcriptome microarray datasets (GSE15471, GSE55643, GSE62165 and GSE91035) were acquired from Gene Expression Omnibus datasets, which included 226 PDAC samples and 65 normal pancreatic tissue samples...
August 2018: Oncology Letters
https://www.readbyqxmd.com/read/30010083/a-two-phase-regulation-of-bone-regeneration-il-17f-mediates-osteoblastogenesis-via-c-ebp-%C3%AE-in-vitro
#13
Yufa Wang, Jieun Kim, Andrea Chan, Cari Whyne, Diane Nam
T lymphocytes and pro-inflammatory cytokines, specifically interleukin-17F (IL-17F) have been identified as important regulators in bone regeneration during fracture repair. To better understand the molecular mechanisms of IL-17F-mediated osteoblastogenesis, a mouse pre-osteoblast cell line (MC3T3-E1) was utilized to characterize the intracellular signal transduction of IL-17F. Comparisons to the established canonical Wnt signaling pathway were made using Wnt3a ligand. Our results demonstrated greater bone marker gene expression in IL-17F-treated cells, compared to cells treated with Wnt3a...
July 17, 2018: Bone
https://www.readbyqxmd.com/read/29998124/canonical-wnt-signaling-promotes-macrophage-proliferation-during-kidney-fibrosis
#14
Ye Feng, Yan Liang, Jiafa Ren, Chunsun Dai
Background: Wnt/β-catenin, an evolutionary conserved signaling pathway, plays an essential role in modulating kidney injury and repair. Our previous studies demonstrated that Wnt/β-catenin signaling could stimulate macrophage M2 polarization and contribute to kidney fibrosis. However, whether canonical Wnt signaling activation leads to macrophage proliferation during kidney fibrosis remains to be determined. Methods: In this study, a mouse model with macrophage-specific β-catenin gene deletion was generated and a unilateral ureter obstruction (UUO) model was created...
June 2018: Kidney Diseases
https://www.readbyqxmd.com/read/29997441/downregulation-of-lncrna-ogfrp1-inhibits-hepatocellular-carcinoma-progression-by-akt-mtor-and-wnt-%C3%AE-catenin-signaling-pathways
#15
Wei Chen, Jia You, Qi Zheng, Yue-Yong Zhu
Introduction: Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) by regulating gene expression. However, the identification of functional lncRNAs in HCC remains insufficient. Our study aimed to investigate the function of lncRNA OGFRP1, which has not been functionally researched before, in Hep3B and HepG2 cells. Methods: lncRNA OGFRP1 in HCC cells was down-regulated by using RNAi technology...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29991769/interaction-of-lef1-with-taz-is-necessary-for-the-osteoblastogenic-activity-of-wnt3a
#16
Jumpei Kida, Kenji Hata, Eriko Nakamura, Hiroko Yagi, Yoshifumi Takahata, Tomohiko Murakami, Yoshinobu Maeda, Riko Nishimura
Canonical Wnt signalling plays an important role in osteoblast differentiation and bone formation. However, the molecular mechanisms by which canonical Wnt signalling exerts its osteoblastogenic effect remain elusive. Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Reporter assay and co-immunoprecipitation experiments revealed functional and physical interaction between LEF1 and TAZ...
July 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29990529/embryoid-body-test-with-morphological-and-molecular-endpoints-implicates-potential-developmental-toxicity-of-trans-resveratrol
#17
Iris Q Kim, Yusuke Marikawa
Developmental toxicity of compounds, which women of reproductive age are exposed to, should be assessed to minimize the incidence of miscarriage and birth defects. The present study examined the potential developmental toxicity of resveratrol, a dietary supplement widely marketed with various health claims, using the P19C5 embryoid body (EB) morphogenesis assay, which evaluates adverse effects of chemical exposures on tissue growth and axial elongation. Resveratrol (trans isoform) impaired morphogenesis at 4 μM and higher, creating smaller and rounder EBs, whereas cis isoform, and glucuronated and sulfonated metabolites did not...
July 7, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29988306/clc-2-knockdown-prevents-cerebrovascular-remodeling-via-inhibition-of-the-wnt-%C3%AE-catenin-signaling-pathway
#18
Jingjing Lu, Feng Xu, Yingna Zhang, Hong Lu, Jiewen Zhang
Background: Mishandling of intracellular chloride (Cl- ) concentration ([Cl- ]i ) in cerebrovascular smooth muscle cells is implicated in several pathological processes, including hyperplasia and remodeling. We investigated the effects of ClC-2-mediated Cl- efflux on the proliferation of human brain vascular smooth muscle cells (HBVSMCs) induced by angiotensin II (AngII). Methods: Cell proliferation and motility were determined using the CCK-8, bromodeoxyuridine staining, wound healing and invasion assays...
2018: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/29986466/label-free-quantitative-proteomics-combined-with-biological-validation-reveals-activation-of-wnt-%C3%AE-catenin-pathway-contributing-to-trastuzumab-resistance-in-gastric-cancer
#19
Wenhu Liu, Jiangbei Yuan, Zhenzhong Liu, Jianwu Zhang, Jinxia Chang
Resistance to trastuzumab, which specifically target HER2-positive breast and gastric cancer, can develop ultimately in cancer patients. However, the underlying mechanisms of resistance in gastric cancer have not been fully elucidated. Here, we established trastuzumab-resistant MKN45 and NCI N87 gastric cancer sublines from their parental cells. The resistant cells exhibited characteristics of epithelial-mesenchymal transition (EMT) and acquired higher migratory and invasive capacities. To exploit the activated pathways and develop new strategies to overcome trastuzumab resistance, we investigated MKN45 and MKN45/R cells via label-free quantitative proteomics, and found pathways that were altered significantly in MKN45/R cells, with the Wnt/β-catenin pathway being the most significant...
July 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29981832/global-gene-expression-analysis-identifies-mef2c-as-a-potential-player-in-wnt16-mediated-transcriptional-regulation
#20
Aimy Sebastian, Nicholas R Hum, Cesar Morfin, Deepa K Murugesh, Gabriela G Loots
Wnt16 is a major Wnt ligand involved in the regulation of postnatal bone homeostasis. Previous studies have shown that Wnt16 promotes bone formation and inhibits bone resorption, suggesting that this molecule could be targeted for therapeutic interventions to treat bone thinning disorders such as osteoporosis. However, the molecular mechanisms by which Wnt16 regulates bone metabolism is not yet fully understood. To better understand the molecular mechanisms by which Wnt16 promotes bone formation and to identify the target genes regulated by Wnt16 in osteoblasts, we treated calvarial osteoblasts purified from C57Bl/6 mice with recombinant Wnt16 and profiled the gene expression changes by RNA-seq at 24 h post-treatment...
July 5, 2018: Gene
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