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https://www.readbyqxmd.com/read/28218291/a-pan-cancer-analysis-of-secreted-frizzled-related-proteins-re-examining-their-proposed-tumour-suppressive-function
#1
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
#2
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...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28153008/correlation-of-blood-bone-turnover-biomarkers-and-wnt-signaling-antagonists-with-as-dish-opll-and-oyl
#3
Chi-Chien Niu, Song-Shu Lin, Li-Jen Yuan, Lih-Huei Chen, Chuen-Yung Yang, An-Ni Chung, Meng-Ling Lu, Tsung-Ting Tsai, Po-Liang Lai, Wen-Jer Chen
BACKGROUND: Wnt signaling plays an important role in development and maintenance of many organs and tissues. The most-studied secreted Wnt inhibitors are sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), and secreted frizzled related protein 1 (SFRP-1) which play important roles in bone turnover. The present study investigated the relationship between serum Wnt inhibitors and diseases with excessive ossification structures, such as ossification of posterior longitudinal ligament (OPLL), ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and ossification of yellow ligament (OYL)...
February 2, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#4
Dorra Elhaj Mahmoud, Nadia Sassi, Ghassen Drissi, Maher Barsaoui, Khaled Zitouna, Hela Sahli, Maryam Kallel-Sellami, Lassad Kanoun, Elhem Cheour, Lilia Laadhar
CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28108510/bone-metastasis-of-prostate-cancer-can-be-therapeutically-targeted-at-the-tbx2-wnt-signaling-axis
#5
Srinivas Nandana, Manisha Tripathi, Peng Duan, Chia-Yi Chu, Rajeev Mishra, Chunyan Liu, Renjie Jin, Hironobu Yamashita, Majd Zayzafoon, Neil A Bhowmick, Haiyen E Zhau, Robert J Matusik, Leland W K Chung
Identification of factors that mediate visceral and bone metastatic spread and subsequent bone remodeling events is highly relevant to successful therapeutic intervention in advanced human prostate cancer (PCa). TBX2, a T-box family transcription factor that negatively regulates cell cycle inhibitor p21, plays critical roles during embryonic development, and recent studies have highlighted its role in cancer. Here we report that TBX2 is overexpressed in human PCa specimens and bone metastases from xenograft mouse models of human PCa...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/27920883/exogenous-secreted-frizzled-related-protein-4-modulates-steroidogenesis-of-rat-granulosa-cells-through-wnt-%C3%AE-catenin-and-pi3k-akt-signaling-pathways
#6
Ghamartaj Hossein, Manijeh Khanmohammadi, Parisa Sahranavard Fard, Yasaman Heidarian, Somaieh Kazemnejad, Mohammad Mehdi Akhondi
BACKGROUND: It has been reported that secreted frizzled-related protein-4 known as an antagonist of Wnt signaling pathway plays a role in luteinization process of rodent granulosa cells. The purpose of this study was twofold: 1) to determine whether recombinant human secreted frizzled-related protein-4 (rhSFRP-4) could directly induce terminal differentiation of rat Granulosa Cells (GCs) and 2) to understand how the modulation of β-catenin and Protein Kinase B (PKB)/AKT activity by exogenous SFRP-4 could be involved in steroidogenesis...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27883247/2-methoxyestradiol-mediated-induction-of-frzb-contributes-to-cell-death-and-autophagy-in-mg63-osteosarcoma-cells
#7
Dalibel Bravo, Kristen L Shogren, Dongqing Zuo, Eric R Wagner, Gobinda Sarkar, Michael J Yaszemski, Avudaiappan Maran
Osteosarcoma is a bone tumor that mainly affects children and adolescents. Although its pathogenesis is still not fully understood, activation of Wnt signaling has been implicated in the development and metastasis of osteosarcoma. In this report, we have investigated the effect of the anti-tumor compound, 2-methoxyestradiol (2-ME) on Wnt antagonist frizzled-related protein b (Frzb), also known as secreted frizzled-related protein (sFRP)3 in human osteosarcoma (MG63) cells. Our results show that 2-ME treatment induces Frzb gene promoter activity, and increases Frzb mRNA and protein levels in osteosarcoma cells...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27871116/glucocorticoid-signaling-and-bone-biology
#8
T Komori
Since glucocorticoids remain an effective therapeutic option for the treatment of many inflammatory and autoimmune diseases, glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. Fractures may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Under physiological conditions, glucocorticoids are required for normal bone development due to their regulation of osteoblast differentiation, possibly via the Wnt/β-catenin pathway and TSC22D3. However, serum levels of endogenous corticosterone are elevated in aged mice and glucocorticoids exert negative effects on the survival of osteoblasts and osteocytes as well as angiogenesis...
November 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/27738322/antagonizing-mir-218-5p-attenuates-wnt-signaling-and-reduces-metastatic-bone-disease-of-triple-negative-breast-cancer-cells
#9
Hanna Taipaleenmäki, Nicholas H Farina, Andre J van Wijnen, Janet L Stein, Eric Hesse, Gary S Stein, Jane B Lian
Wnt signaling is implicated in bone formation and activated in breast cancer cells promoting primary and metastatic tumor growth. A compelling question is whether osteogenic miRNAs that increase Wnt activity for bone formation are aberrantly expressed in breast tumor cells to support metastatic bone disease. Here we report that miR-218-5p is highly expressed in bone metastases from breast cancer patients, but is not detected in normal mammary epithelial cells. Furthermore, inhibition of miR-218-5p impaired the growth of bone metastatic MDA-MB-231 cells in the bone microenvironment in vivo...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27659069/methylation-of-sfrp2-gene-as-a-promising-noninvasive-biomarker-using-feces-in-colorectal-cancer-diagnosis-a-systematic-meta-analysis
#10
Qihua Yang, Tao Huang, Guoliang Ye, Bojun Wang, Xinjun Zhang
Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported. However, the diagnostic role of SFRP methylation in colorectal cancer (CRC) remains unclear. A systematic search was performed to identify eligible articles for analysis. The pooled OR showed that SFRP1, SFRP2, SFRP4 and SFRP5 methylation was significantly higher in CRC and benign mucosal lesions than in normal colonic mucosa. When CRC was compared to benign mucosal lesions, SFRP1 and SFRP2 methylation had a significantly higher OR, but methylated SFRP4 and SFRP5 had a similar OR...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27599467/the-expression-of-sfrp1-sfrp3-dvl1-and-dvl2-proteins-in-testicular-germ-cell-tumors
#11
Dora Fabijanovic, Iris Zunic, Tamara Nikuseva Martic, Faruk Skenderi, Ljiljana Serman, Semir Vranic
Germ cell tumors of the testis are a heterogeneous group of neoplasms that affect male adolescents and young adults. Wnt signaling pathway components have been shown to be actively involved in normal and malignant germ cell differentiation and progression. In this study, we aimed to explore the expression patterns of the secreted frizzled-related protein (SFRP) and Disheveled protein family (DVL) in a subset of testicular germ cell tumors. Eighty-five formalin-fixed, paraffin-embedded tissue samples of the primary germ cell tumors of the testis were stained against SFRP1, SFRP3, DVL1, and DVL2 proteins using immunohistochemistry...
November 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27570179/sfrp1-repression-in-prostate-cancer-is-triggered-by-two-different-epigenetic-mechanisms
#12
Pilar García-Tobilla, Susana R Solórzano, Iván Salido-Guadarrama, Vanessa González-Covarrubias, Gustavo Morales-Montor, Carlos E Díaz-Otañez, Mauricio Rodríguez-Dorantes
Worldwide, prostate cancer (PCa) is the second cause of death from malignant tumors among men. Establishment of aberrant epigenetic modifications, such as histone post-translational modifications (PTMs) and DNA methylation (DNAme) produce alterations of gene expression that are common in PCa. Genes of the SFRP family are tumor suppressor genes that are frequently silenced by DNA hypermethylation in many cancer types. The SFRP family is composed of 5 members (SFRP1-5) that modulate the WNT pathway, which is aberrantly activated in PCa...
November 30, 2016: Gene
https://www.readbyqxmd.com/read/27346542/wnt-frizzled-and-sfrp-gene-expression-patterns-during-gastrulation-in-the-starfish-patiria-asterina-pectinifera
#13
Narudo Kawai, Ritsu Kuraishi, Hiroyuki Kaneko
By the initial phase of gastrulation, Wnt pathway regulation mediates endomesoderm specification and establishes the animal-vegetal axis, thereby leading to proper gastrulation in starfish. To provide insight into the ancestral mechanism regulating deuterostome gastrulation, we identified the gene expression patterns of Wnt, Frizzled (Fz), and secreted frizzled-related protein (sFRP) family genes, which play a role in the initial stage of the Wnt pathway, in starfish Patiria (Asterina) pectinifera embryos using whole mount in situ hybridization...
May 2016: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/27327904/parenchyma-stromal-interactions-induce-fibrosis-by-secreting-ccn2-and-promote-osteoclastogenesis-by-stimulating-rankl-and-cd68-through-activated-tgf-%C3%AE-bmp4-in-ameloblastoma
#14
Yuichiro Takebe, Hidetsugu Tsujigiwa, Naoki Katase, Chong Huat Siar, Kiyofumi Takabatake, Masae Fujii, Ryo Tamamura, Keisuke Nakano, Hitoshi Nagatsuka
BACKGROUND: Tumor parenchyma-stromal interactions affect the properties of tumors and their dynamics. Our group previously showed that secreted frizzled related protein (sFRP)-2 impairs bone formation and promotes bone invasion in ameloblastoma. However, the effects of the secreted growth factors CCN2, TGF-β, and BMP4 on stromal tissues in ameloblastoma remain unclear. MATERIALS AND RESULTS: Thirty-five paraffin-embedded ameloblastoma cases, ameloblastoma-derived cell lines (AM-1), and primary cultures of ameloblastoma stromal fibroblasts (ASF) were used...
January 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/27165410/il-17a-deficiency-promotes-periosteal-bone-formation-in-a-model-of-inflammatory-arthritis
#15
Anita T Shaw, Yukiko Maeda, Ellen M Gravallese
BACKGROUND: Interleukin-17A (IL-17A) plays a pathogenic role in several rheumatic diseases including spondyloarthritis and, paradoxically, has been described to both promote and protect from bone formation. We therefore examined the effects of IL-17A on osteoblast differentiation in vitro and on periosteal bone formation in an in vivo model of inflammatory arthritis. METHODS: K/BxN serum transfer arthritis was induced in IL-17A-deficient and wild-type mice. Clinical and histologic inflammation was assessed and periosteal bone formation was quantitated...
May 10, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27129770/secreted-frizzled-related-protein-2-sfrp2-redirects-non-canonical-wnt-signaling-from-fz7-to-ror2-during-vertebrate-gastrulation
#16
Eva-Maria Brinkmann, Benjamin Mattes, Rahul Kumar, Anja I H Hagemann, Dietmar Gradl, Steffen Scholpp, Herbert Steinbeisser, Lilian T Kaufmann, Suat Özbek
Convergent extension movements during vertebrate gastrulation require a balanced activity of non-canonical Wnt signaling pathways, but the factors regulating this interplay on the molecular level are poorly characterized. Here we show that sFRP2, a member of the secreted frizzled-related protein (sFRP) family, is required for morphogenesis and papc expression during Xenopus gastrulation. We further provide evidence that sFRP2 redirects non-canonical Wnt signaling from Frizzled 7 (Fz7) to the receptor tyrosine kinase-like orphan receptor 2 (Ror2)...
June 24, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27114416/field-cancerization-in-sporadic-colon-cancer
#17
Soo-Kyung Park, Chang Seok Song, Hyo-Joon Yang, Yoon Suk Jung, Kyu Yong Choi, Dong Hoe Koo, Kyung Eun Kim, Kyung Uk Jeong, Hyung Ook Kim, Hungdai Kim, Ho-Kyung Chun, Dong Il Park
BACKGROUND/AIMS: Aberrant DNA methylation has a specific role in field cancerization. Certain molecular markers, including secreted frizzled-related protein 2 (SFRP2), tissue factor pathway inhibitor 2 (TFPI2 ), N-Myc downstream-regulated gene 4 (NDRG4) and bone morphogenic protein 3 (BMP3), have previously been shown to be hypermethylated in colorectal cancer (CRC). We aim to examine field cancerization in CRC based on the presence of aberrant DNA methylation in normal-appearing tissue from CRC patients...
September 15, 2016: Gut and Liver
https://www.readbyqxmd.com/read/27063405/sfrp-mediated-wnt-sequestration-as-a-potential-therapeutic-target-for-alzheimer-s-disease
#18
REVIEW
Sudha Warrier, Raja Marimuthu, Sreeja Sekhar, G Bhuvanalakshmi, Frank Arfuso, Anjan Kumar Das, Ramesh Bhonde, Ralph Martins, Arun Dharmarajan
The extracellular ligand, Wnt, and its receptors are involved in sign al transduction and play an important role in axis formation and neural development. In neurodegenerative disorders such as Alzheimer's disease (AD), a decrease of the intracellular Wnt effector, β-catenin, has been linked to amyloid-β-peptide-induced neurotoxicity. Despite this knowledge, targeting Wnt inhibitors as potential biomarkers has not been explored, and harnessing Wnt activators as therapeutic candidates remains largely not investigated...
June 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27019073/sfrp5-associates-with-beta-cell-function-in-humans
#19
Maren Carstensen-Kirberg, Erifili Hatziagelaki, Anastasia Tsiavou, Athina Chounta, Peter Nowotny, Giovanni Pacini, George Dimitriadis, Michael Roden, Christian Herder
BACKGROUND: Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans. MATERIAL AND METHODS: This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT...
June 2016: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26958939/adipocytes-wnt5a-mediated-dedifferentiation-a-possible-target-in-pancreatic-cancer-microenvironment
#20
Elena Zoico, Elena Darra, Vanni Rizzatti, Simona Budui, Guido Franceschetti, Gloria Mazzali, Andrea P Rossi, Francesco Fantin, Marta Menegazzi, Saverio Cinti, Mauro Zamboni
A significant epidemiological association between obesity and pancreatic ductal adenocarcinoma (PDAC) has previously been described, as well as a correlation between the degree of pancreatic steatosis, PDAC risk and prognosis. The underlying mechanisms are still not completely known.After co-culture of 3T3-L1 adipocytes and MiaPaCa2 with an in vitro transwell system we observed the appearance of fibroblast-like cells, along with a decrease in number and size of remaining adipocytes. RT-PCR analyses of 3T3-L1 adipocytes in co-culture showed a decrease in gene expression of typical markers of mature adipocytes, in parallel with an increased expression of fibroblast-specific and reprogramming genes...
April 12, 2016: Oncotarget
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