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https://www.readbyqxmd.com/read/28883539/role-of-adipose-tissue-in-melanoma-cancer-microenvironment-and-progression
#1
E Zoico, E Darra, V Rizzatti, M Tebon, G Franceschetti, G Mazzali, A P Rossi, F Fantin, M Zamboni
BACKGROUND: An epidemiological association between excess weight and increased risk of cancer has been described in melanoma, for which the physiopathological mechanisms are still unknown. The study of tumor microenvironment and of the role of adipocytes in cancer development, progression and metastasis has recently received great interest. However, the role of peritumoral adipocytes has been characterized only in a few types of cancer and in melanoma it still remains to be defined. METHODS: We investigated the interactions between adipocytes and melanoma cells using an in vitro co-culture system...
September 8, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28851362/inverse-associations-between-serum-levels-of-secreted-frizzled-related-protein-5-sfrp5-and-multiple-cardiometabolic-risk-factors-kora-f4-study
#2
Maren Carstensen-Kirberg, Julia M Kannenberg, Cornelia Huth, Christa Meisinger, Wolfgang Koenig, Margit Heier, Annette Peters, Wolfgang Rathmann, Michael Roden, Christian Herder, Barbara Thorand
AIMS: Secreted frizzled-related protein (Sfrp)5 has beneficial effects on insulin sensitivity, inflammation and cardiovascular risk in different mouse models, but its relevance for cardiometabolic diseases in humans is controversial. We aimed to characterise associations of circulating SFRP5 with cardiometabolic risk factors and prediabetes/type 2 diabetes in a large population-based cohort. METHODS: Cross-sectional associations between serum SFRP5 and cardiometabolic risk factors as well as prediabetes/type 2 diabetes were investigated in 1096 participants aged 62-81 years from the German KORA F4 study, of whom 666 had prediabetes or type 2 diabetes...
August 29, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28808056/the-crystal-structure-of-full-length-sizzled-from-xenopus-laevis-yields-insights-into-wnt-antagonistic-function-of-secreted-frizzled-related-proteins
#3
Qixin Bu, Zhiqiang Li, Junying Zhang, Fei Xu, Jianmei Liu, Heli Liu
The Wnt signaling pathway is crucial to cell proliferation, differentiation and migration. The secreted frizzled-related proteins (sFRPs) represent the largest family of secreted Wnt inhibitors. However, their function in antagonizing Wnt signaling has remained somewhat controversial. Here we report the crystal structure of Sizzled from Xenopus laevis, the first full-length structure of an sFRP. Tethered by an inter-domain disulfide bond and a linker, the N-terminal CRD domain and the C-terminal NTR domain of Sizzled are arranged in a tandem fashion, with the NTR domain occluding the groove of CRD for Wnt accessibility...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28790854/hypermethylation-of-secreted-frizzled-related-proteins-predicts-poor-prognosis-in-non-m3-acute-myeloid-leukemia
#4
Hong Guo, Ting-Juan Zhang, Xiang-Mei Wen, Jing-Dong Zhou, Ji-Chun Ma, Cui An, Wei Zhang, Zi-Jun Xu, Jiang Lin, Jun Qian
OBJECTIVE: Secreted frizzled-related proteins (SFRPs) as Wnt signaling antagonists have been found to be dysregulated by promoter hypermethylation in several cancers including acute myeloid leukemia (AML). This study aimed to investigate the methylated status of SFRPs promoter region and its clinical relevance in Chinese non-M3 AML patients. METHODS: SFRPs methylation in 139 primary non-M3 AML patients was determined using methylation-specific real-time quantitative polymerase chain reaction...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28711237/precise-role-of-dermal-fibroblasts-on-melanocyte-pigmentation
#5
REVIEW
Yinjuan Wang, Céline Viennet, Sophie Robin, Jean-Yves Berthon, Li He, Philippe Humbert
Dermal fibroblasts are traditionally recognized as synthesizing, remodeling and depositing collagen and extracellular matrix, the structural framework for tissues, helping to bring thickness and firmness to the skin. However, the role of fibroblasts on skin pigmentation arouses concern recently. More is known about the interactions between epidermal melanocytes and keratinocytes. This review highlights the importance of fibroblast-derived melanogenic paracrine mediators in the regulation of melanocyte activities...
July 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28694840/hepatic-adipocyte-enteric-and-pancreatic-hormones-response-to-dietary-macronutrient-composition-and-relationship-with-metabolism
#6
Bridget M Hron, Cara B Ebbeling, Henry A Feldman, David S Ludwig
BACKGROUND: We sought to characterize the effects of dietary macronutrient composition on various hormones implicated in the regulation of insulin sensitivity (IS) and energy expenditure (EE). METHODS: Following 10-15% weight loss, 21 overweight subjects consumed 3 weight-loss maintenance diets [low fat (LF), low glycemic index (LGI) and very low carbohydrate (VLC)] in random order, each for 4 weeks. At baseline and at the end of each treatment period, fasting samples for fibroblast growth factor (FGF)-21, heme-oxygenase-1 (HO-1), chemerin, irisin, secreted frizzle-related protein (SFRP-4), total bile acids, ghrelin, gastrin inhibitory peptide (GIP), peptide-Y, and amylin; hepatic and peripheral IS; and EE were obtained...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28643146/helicobacter-pylori-induced-modulation-of-the-promoter-methylation-of-wnt-antagonist-genes-in-gastric-carcinogenesis
#7
Hyo-Joon Yang, Sang Gyun Kim, Joo Hyun Lim, Ji Min Choi, Woo Ho Kim, Hyun Chae Jung
BACKGROUND: This study aimed to investigate the changes in the promoter methylation and gene expression of multiple Wnt antagonists between the chronic infection and eradication of Helicobacter pylori (H. pylori) in gastric carcinogenesis. METHODS: The levels of methylation and corresponding mRNA expression of seven Wnt antagonist genes (SFRP1, -2, -5, DKK1, -2, -3, WIF1) were compared among the patients with H. pylori-positive gastric cancers (GCs), and H. pylori-positive and H...
June 22, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28589318/matricellular-proteins-in-cancer-a-focus-on-secreted-frizzled-related-proteins
#8
Krista Marie Vincent, Lynne-Marie Postovit
Tumours are complex entities, wherein cancer cells interact with myriad soluble, insoluble and cell associated factors. These microenvironmental mediators regulate tumour growth, progression and metastasis, and are produced by cancer cells and by stromal components such as fibroblast, adipocytes and immune cells. Through their ability to bind to extracellular matrix proteins, cell surface receptors and growth factors, matricellular proteins enable a dynamic reciprocity between cancer cells and their microenvironment...
June 7, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28533339/structure-based-prediction-of-wnt-binding-affinities-for-frizzled-type-cysteine-rich-domains
#9
Mark Agostino, Sebastian Öther-Gee Pohl, Arun Dharmarajan
Wnt signaling pathways are of significant interest in development and oncogenesis. The first step in these pathways typically involves the binding of a Wnt protein to the cysteine-rich domain (CRD) of a Frizzled receptor. Wnt-Frizzled interactions can be antagonized by secreted Frizzled-related proteins (SFRPs), which also contain a Frizzled-like CRD. The large number of Wnts, Frizzleds, and SFRPs, as well as the hydrophobic nature of Wnt, poses challenges to laboratory-based investigations of interactions involving Wnt...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28424479/wnt-%C3%AE-catenin-signaling-pathway-a-major-player-in-the-injury-induced-fibrosis-and-dysfunction-of-the-external-anal-sphincter
#10
M Raj Rajasekaran, Sadhana Kanoo, Johnny Fu, Valmik Bhargava, Ravinder K Mittal
Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. Our goal was to examine the role of Wnt pathway in the external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New Zealand White female rabbits were subjected to surgical EAS myotomy and administered local injections of either a Wnt antagonist (sFRP-2; daily for 7 days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured for 15 weeks after which the animals were sacrificed...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28398872/hydrogen-peroxide-induced-secreted-frizzled-related-protein-1-gene-demethylation-contributes-to-hydrogen-peroxide-induced-apoptosis-in-human-u251-glioma-cells
#11
Zhiguo Xing, Yaping Ni, Junjie Zhao, Xudong Ma
Glioblastoma multiforme is a type of central nervous system tumor with extremely poor prognosis. Previously, hydrogen peroxide (H2O2), which promotes the oxidative stress response, has been reported to induce the apoptosis of glioma cells. Recently, secreted frizzled-related protein 1 (SFRP1) has been shown to be associated with various types of malignant tumors and with H2O2-induced oxidative stress in cardiomyocytes by negatively regulating the Wnt signaling pathway. This study aimed to explore SFRP1 expression and its roles in H2O2-induced apoptosis in human glioma cells...
May 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28373842/breast-cancer-stem-like-cells-are-inhibited-by-diosgenin-a-steroidal-saponin-by-the-attenuation-of-the-wnt-%C3%AE-catenin-signaling-via-the-wnt-antagonist-secreted-frizzled-related-protein-4
#12
G Bhuvanalakshmi, Basappa, Kanchugarakoppal S Rangappa, Arun Dharmarajan, Gautam Sethi, Alan P Kumar, Sudha Warrier
Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of chemo- and radio-resistant stem-like cells, termed as the cancer stem cells (CSCs) and their eradication could significantly enhance clinical outcomes. Most of the presently administered chemotherapeutics target the tumor bulk but are ineffective against the CSCs. We report here that diosgenin (DG), a naturally occurring steroidal saponin, could effectively inhibit CSCs from three breast cancer cell lines, MCF7, T47D and MDA-MB-231, by inducing apoptosis and inhibiting the CSC associated phenotypes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28368424/p53-rb-inhibition-induces-metastatic-adrenocortical-carcinomas-in-a-preclinical-transgenic-model
#13
M Batisse-Lignier, I Sahut-Barnola, F Tissier, T Dumontet, M Mathieu, C Drelon, J-C Pointud, C Damon-Soubeyrand, G Marceau, J-L Kemeny, J Bertherat, I Tauveron, P Val, A Martinez, A-M Lefrançois-Martinez
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/β-catenin signaling pathways as main contributors to the disease. However, isolated β-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28346008/wnt-%C3%AE-catenin-signaling-is-required-for-distraction-osteogenesis-in-rats
#14
Xuemei Wang, En Luo, Ruiye Bi, Bin Ye, Jing Hu, Shujuan Zou
OVERVIEW: The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven't been well characterized. MATERIALS AND METHODS: We established a DO model using Sprague-Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process...
March 1, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28333280/hcg-activates-epac-erk1-2-signaling-regulating-progesterone-receptor-expression-and-function-in-human-endometrial-stromal-cells
#15
Alejandro Tapia-Pizarro, Sebastián Archiles, Felipe Argandoña, Cecilia Valencia, Keyla Zavaleta, M Cecilia Johnson, Reinaldo González-Ramos, Luigi Devoto
STUDY QUESTION: How does hCG signal in human endometrial stromal cells (ESCs) and what is its role in regulating ESC function? SUMMARY ANSWER: hCG signaling in ESCs activates the extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) pathway through exchange protein activated by cyclic AMP (cAMP) (Epac) and transiently increases progesterone receptor (PR) transcript and protein expression and its transcriptional function. WHAT IS KNOWN ALREADY: hCG is one of the earliest embryo-derived secreted signals in the endometrium, which abundantly expresses LH/hCG receptors...
June 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#16
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Xiaoyan Bai, Jing Nie
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 16, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28292423/a-wnt5-activity-asymmetry-and-intercellular-signaling-via-pcp-proteins-polarize-node-cells-for-left-right-symmetry-breaking
#17
Katsura Minegishi, Masakazu Hashimoto, Rieko Ajima, Katsuyoshi Takaoka, Kyosuke Shinohara, Yayoi Ikawa, Hiromi Nishimura, Andrew P McMahon, Karl Willert, Yasushi Okada, Hiroshi Sasaki, Dongbo Shi, Toshihiko Fujimori, Toshihisa Ohtsuka, Yasunobu Igarashi, Terry P Yamaguchi, Akihiko Shimono, Hidetaka Shiratori, Hiroshi Hamada
Polarization of node cells along the anterior-posterior axis of mouse embryos is responsible for left-right symmetry breaking. How node cells become polarized has remained unknown, however. Wnt5a and Wnt5b are expressed posteriorly relative to the node, whereas genes for Sfrp inhibitors of Wnt signaling are expressed anteriorly. Here we show that polarization of node cells is impaired in Wnt5a(-/-)Wnt5b(-/-) and Sfrp mutant embryos, and also in the presence of a uniform distribution of Wnt5a or Sfrp1, suggesting that Wnt5 and Sfrp proteins act as instructive signals in this process...
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28273499/secreted-frizzled-related-protein-2-mediated-cancer-events-friend-or-foe
#18
REVIEW
Yanhui Liu, Qun Zhou, Dexi Zhou, Cheng Huang, Xiaoming Meng, Jun Li
Secreted frizzled-related protein (SFRP)2, an identified member of the SFRPs family of molecules, is often methylated in human cancers and its down-regulation is closely related to Wnt signaling activity and tumor progression. Although the blocker of the Wnt signaling has not been fully used in clinical trial, interest has been further enhanced by the realization of SFRPs' potential as targets to modulate Wnt signaling and cancer cell growth. Emerging evidence showed that SFRP2 was an anti-oncogene, however, a steady flow of research has indicated that it may also have tumor promotion effects in some cancer types...
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28218291/a-pan-cancer-analysis-of-secreted-frizzled-related-proteins-re-examining-their-proposed-tumour-suppressive-function
#19
Krista Marie Vincent, Lynne-Marie Postovit
Secreted frizzled-related proteins (SFRPs), containing five family members (SFRPs 1-5) are putative extracellular Wnt inhibitors. Given their abilities to inhibit Wnt signalling, as well as the loss of SFRP1 in many cancers, this family is generally considered to be tumour suppressive. In this study we analyzed gene expression, promoter methylation and survival data from over 8000 tumour and normal samples from 29 cancers in order to map the context-specific associations of SFRPs 1-5 with patient survival, gene silencing and gene expression signatures...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209772/maternal-smoke-exposure-decreases-mesenchymal-proliferation-and-modulates-rho-gtpase-dependent-actin-cytoskeletal-signaling-in-fetal-lungs
#20
Uchenna Unachukwu, Jordis Trischler, Monica Goldklang, Rui Xiao, Jeanine D'Armiento
The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m(3)) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection...
June 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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