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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
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
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
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
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
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...
June 21, 2016: Journal of Oral Pathology & Medicine
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...
2016: Arthritis Research & Therapy
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
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
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
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
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
Chengbo Xu, Jianzhen Shen, Bin Liao, Haiying Fu, Huarong Zhou, Yan Qi, Zhenping Huangfu, Yining Chen, Jiawei Chen
OBJECTIVE: To study the promoter methylation status of SFRP genes and the effect of 5- aza- 2'- deoxycytidine (5- Aza- CdR)induced apoptosis via Wnt/β- catenin pathway by demethylation in Jurkat cells. METHODS: Jurkat cells were treated with different concentrations of 5- Aza- CdR. The cell proliferation level of Jurkat cells was detected by MTT assay. Apoptosis was evaluated by flow cytometry. Methylation- spcific PCR (MSP) was used to determine the methylation status of SFRP genes...
January 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Jeannine Hoepfner, Mandy Kleinsorge, Oliver Papp, Mania Ackermann, Susanne Alfken, Ursula Rinas, Wladimir Solodenko, Andreas Kirschning, Malte Sgodda, Tobias Cantz
Pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) are of great promise in regenerative medicine, including molecular studies of disease mechanisms, if the affected cell type can be authentically generated during in vitro differentiation. Most existing protocols aim to mimic embryonic development steps by the supplementation of specific cytokines and small molecules, but the involved signaling pathways need further exploration. In this study, we investigated enhanced initial activation of Wnt signaling for definitive endoderm formation and subsequent rapid shutdown of Wnt signaling for proper foregut endoderm specification using 3 μM CHIR99021 and 0...
May 2016: Cell Biology International
Azadeh Yeganeh, Carla G Taylor, Jenna Poole, Leslee Tworek, Peter Zahradka
BACKGROUND: Trans-10, cis-12 (t10-c12) CLA treatment reduces lipid accumulation in differentiating mouse and human adipocytes, and decreases fat mass in mice, yet the mechanism of action remains unknown. OBJECTIVE: This study investigated the effect of the cis-9, trans-11 (c9-t11) and t10-c12 CLA isomers on the Wnt/β-catenin pathway, which has been reported to inhibit adipogenesis by down-regulating PPARγ. RESULTS: We observed that t10-c12 CLA treatment of 3T3-L1 adipocytes increases the levels of β-catenin and Ser-675 phosphorylated β-catenin due to inhibition of its degradation...
April 2016: Biochimica et Biophysica Acta
Alisa Boucsein, Jonas Benzler, Cindy Hempp, Sigrid Stöhr, Gisela Helfer, Alexander Tups
The WNT pathway was shown to play an important role in the adult central nervous system. We previously identified the WNT pathway as a novel integration site of the adipokine leptin in mediating its neuroendocrine control of metabolism in obese mice. Here we investigated the implication of WNT signaling in seasonal body weight regulation exhibited by the Djungarian hamster (Phodopus sungorus), a seasonal mammal that exhibits profound annual changes in leptin sensitivity. We furthermore investigated whether crucial components of the WNT pathway are regulated in a diurnal manner...
February 2016: Endocrinology
Jorge Parodi, Carla Montecinos-Oliva, Rodrigo Varas, Iván E Alfaro, Felipe G Serrano, Manuel Varas-Godoy, Francisco J Muñoz, Waldo Cerpa, Juan A Godoy, Nibaldo C Inestrosa
Hippocampal synapses play a key role in memory and learning processes by inducing long-term potentiation and depression. Wnt signaling is essential in the development and maintenance of synapses via several mechanisms. We have previously found that Wnt5a induces the production of nitric oxide (NO), which modulates NMDA receptor expression in the postsynaptic regions of hippocampal neurons. Here, we report that Wnt5a selectively inhibits a voltage-gated K(+) current (Kv current) and increases synaptic activity in hippocampal slices...
September 2015: Molecular and Cellular Neurosciences
Jing Tao, Bang-dang Chen, Yi-tong Ma, Yi-ning Yang, Xiao-mei Li, Xiang Ma, Zi-xiang Yu, Fen Liu, Yang Xiang, You Chen
BACKGROUND: Lately, there is accumulating evidence that the Wnt/Frizzled pathway is reactivated after myocardial infarction, the inhibition of the pathway is beneficial since it reduce of myocardial apoptosis and prevents heart failure. FrzA/Sfrp-1, a secreted frizzled-related protein and antagonist for the wnt/frizzled pathway. We assessed the hypothesis that FrzA protects cardiomyocytes from H2O2-Induced Oxidative damage through the inhibition of Wnt/Frizzled pathway activity. METHODS: We used a recombinant AAV9 vector to deliver FrzA gene into neonatal rat ventricle myocytes and developed an oxidative stress model using H2O2...
2015: Lipids in Health and Disease
Bettina Oehrle, Gerald Burgstaller, Martin Irmler, Stefan Dehmel, Jessica Grün, Tiffany Hwang, Susanne Krauss-Etschmann, Johannes Beckers, Silke Meiners, Oliver Eickelberg
The invasion of activated fibroblasts represents a key pathomechanism in fibrotic diseases, carcinogenesis and metastasis. Invading fibroblasts contribute to fibrotic extracellular matrix (ECM) formation and the initiation, progression, or resistance of cancer. To construct transcriptome-wide signatures of fibroblast invasion, we used a multiplex phenotypic 3D invasion assay using lung fibroblasts. Microarray-based gene expression profiles of invading and non-invading fibroblasts demonstrated that 1,049 genes were differentially regulated (>1...
2015: Scientific Reports
Baruch Frenkel, Wendy White, Jan Tuckermann
Osteoporosis is among the most devastating side effects of glucocorticoid (GC) therapy for the management of inflammatory and auto-immune diseases. Evidence from both humans and mice indicate deleterious skeletal effects within weeks of pharmacological GC administration, both related and unrelated to a decrease in bone mineral density (BMD). Osteoclast numbers and bone resorption are also rapidly increased, and together with osteoblast inactivation and decreased bone formation, these changes lead the fastest loss in BMD during the initial disease phase...
2015: Advances in Experimental Medicine and Biology
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