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wnt frizzled

Claire Peghaire, Marie Lise Bats, Raj Sewduth, Sylvie Jeanningros, Beatrice Jaspard, Thierry Couffinhal, Cécile Duplàa, Pascale Dufourcq
OBJECTIVE: Vessel formation requires precise orchestration of a series of morphometric and molecular events controlled by a multitude of angiogenic factors and morphogens. Wnt/frizzled signaling is required for proper vascular formation. In this study, we investigated the role of the Fzd7 (frizzled-7) receptor in retinal vascular development and its relationship with the Wnt/β-catenin canonical pathway and Notch signaling. APPROACH AND RESULTS: Using transgenic mice, we demonstrated that Fzd7 is required for postnatal vascular formation...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Ritva Heljasvaara, Mari Aikio, Heli Ruotsalainen, Taina Pihlajaniemi
Collagen XVIII is a ubiquitous basement membrane (BM) proteoglycan produced in three tissue-specific isoforms that differ in their N-terminal non-collagenous sequences, but share collagenous and C-terminal non-collagenous domains. The collagenous domain provides flexibility to the large collagen XVIII molecules on account of multiple interruptions in collagenous sequences. Each isoform has a complex multi-domain structure that endows it with an ability to perform various biological functions. The long isoform contains a frizzled-like (Fz) domain with Wnt-inhibiting activity and a unique domain of unknown function (DUF959), which is also present in the medium isoform...
October 13, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Melissa V Gammons, Trevor J Rutherford, Zachary Steinhart, Stephane Angers, Mariann Bienz
Dishevelled (DVL) assembles Wnt signalosomes through dynamic head-to-tail polymerisation by means of its DIX domain. It thus transduces Wnt signals to cytoplasmic effectors including β-catenin, to control cell fates during normal development, tissue homeostasis and also in cancer. To date, most functional studies of Dishevelled relied on its Wnt-independent signalling activity resulting from overexpression, which is sufficient to trigger polymerisation, bypassing the requirement for Wnt signals. Here, we generate a human cell line devoid of endogenous Dishevelled (DVL1- DVL3), which lacks Wnt signal transduction to β-catenin...
October 15, 2016: Journal of Cell Science
Juan Wu, Junfeng Zhang, Qinhong Cao, Junqin Wang, Zhen Zhan, Zhong Li
BACKGROUND: Secreted frizzled-related protein 1 (sFRP1), a negative regulator of the Wnt signaling pathway, is frequently inactivated in human gastric cancer. Genetic variants in the 3' untranslated region (UTR) of the gene may influence the strength of miRNA binding and the regulation of mRNA transcription, affecting the individual's cancer risk. This study aims to investigate the impact of variants in the 3' UTR of sFRP1 on the gastric cancer susceptibility in a Chinese population. PATIENTS AND METHODS: The association between 2 sFRP1 gene variation loci (rs1127379 and rs10088390) with minor allele frequency more than 0...
October 10, 2016: International Journal of Biological Markers
James C Lin, Wei-Wen Kuo, Rathinasamy Baskaran, Ming-Cheng Chen, Tsung-Jung Ho, Ray-Jade Chen, Ya-Fang Chen, Viswanadha Vijaya Padma, Ing-Shiow Lay, Chih-Yang Huang
BACKGROUND: Beta-catenin has been implicated in cell-cell communication in a wide variety of developmental and physiological processes. Defective Wnt signaling could result in various cardiac and vascular abnormalities. Little is known regarding Wnt/frizzled pathway in cardiomyocyte apoptosis. METHODS: In this study, the role of β-catenin in apoptosis was investigated in H9c2 cardiomyocytes and primary cardiomyocytes isolated in diabetic Wistar rats. The cardiomyocytes were transfected with porcine cytomegalovirus (pCMV)-β-catenin plasmid in order to overexpress β-catenin...
October 13, 2016: Cardiology Journal
Leilei Zhong, Xiaobin Huang, Emilie Dooms Rodrigues, Jeroen Leijten, Theo Verrips, Mohamed El Khattabi, Marcel Karperien, Janine N Post
Hypertrophic differentiation occurs during in vitro chondrogenesis of mesenchymal stem cells (MSCs), decreasing the quality of the cartilage construct. Previously we identified WNT pathway antagonists Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) as key factors in blocking hypertrophic differentiation of hMSCs. In this study, we investigated the role of endogenously expressed DKK1 and FRZB in chondrogenesis of hMSC, chondrocyte redifferentiation and in preventing cell hypertrophy using three relevant human cell based systems, isolated hMSCs, isolated primary human chondrocytes (hChs), and co-cultures of hMSCs with hChs for which we specifically designed neutralizing nano-antibodies...
October 12, 2016: Stem Cells and Development
Yanhui Liu, Zhenghao Sun, Dandan Xu, Junda Liu, Xiaofeng Li, Xiaoqin Wu, Yilong Zhang, Qianqian Wang, Cheng Huang, Xiaoming Meng, Jun Li
Hesperidin (HDN), a flavanone glycoside derived from the citrus cultivation, has a multitude of pharmacological properties, which include antioxidant, anti-inflammatory, hypolipidaemic and anti-carcinogenic actions, but the underlying mechanisms by which treatment of HDN attenuates Rheumatoid Arthritis (RA) remain elusive. Here we engaged to determine whether Hesperidin derivative-11(HDND-11), a HDN derivative with enhanced water-solubility and bioavailability, is effective on treating arthritis in rats. In this study, results of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetra-zolium bromide (MTT) assay and Flow cytometry indicated that administration of HDND-11 inhibited proliferation of fibroblast-like synoviocytes (FLS)...
October 6, 2016: European Journal of Pharmacology
Alana M Chin, Yu-Hwai Tsai, Stacy R Finkbeiner, Melinda S Nagy, Emily M Walker, Nicole J Ethen, Bart O Williams, Michele A Battle, Jason R Spence
Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13...
October 6, 2016: Stem Cell Reports
Melissa V Gammons, Miha Renko, Christopher M Johnson, Trevor J Rutherford, Mariann Bienz
Extracellular signals are often transduced by dynamic signaling complexes ("signalosomes") assembled by oligomerizing hub proteins following their recruitment to signal-activated transmembrane receptors. A paradigm is the Wnt signalosome, which is assembled by Dishevelled via reversible head-to-tail polymerization by its DIX domain. Its activity causes stabilization of β-catenin, a Wnt effector with pivotal roles in animal development and cancer. How Wnt triggers signalosome assembly is unknown. Here, we use structural analysis, as well as biophysical and cell-based assays, to show that the DEP domain of Dishevelled undergoes a conformational switch, from monomeric to swapped dimer, to trigger DIX-dependent polymerization and signaling to β-catenin...
October 6, 2016: Molecular Cell
Liang Tao, Jie Zhang, Paul Meraner, Alessio Tovaglieri, Xiaoqian Wu, Ralf Gerhard, Xinjun Zhang, William B Stallcup, Ji Miao, Xi He, Julian G Hurdle, David T Breault, Abraham L Brass, Min Dong
Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium...
September 28, 2016: Nature
Giacomo Lettini, Lorenza Sisinni, Valentina Condelli, Danilo Swann Matassa, Vittorio Simeon, Francesca Maddalena, Marica Gemei, Elvira Lopes, Giulia Vita, Luigi Del Vecchio, Franca Esposito, Matteo Landriscina
Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. Indeed, treatment failures are triggered by cancer stem cells (CSCs) that give rise to tumor repopulation upon initial remission. Thus, the role of the heat shock protein TRAP1 in stemness was investigated in CRC cell lines and human specimens, based on its involvement in colorectal carcinogenesis, through regulation of apoptosis, protein homeostasis and bioenergetics. Strikingly, co-expression between TRAP1 and stem cell markers was observed in stem cells located at the bottom of intestinal crypts and in CSCs sorted from CRC cell lines...
November 1, 2016: Cell Death and Differentiation
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
Andrew P Hinck, Thomas D Mueller, Timothy A Springer
We review the evolution and structure of members of the transforming growth factor β (TGF-β) family, antagonistic or agonistic modulators, and receptors that regulate TGF-β signaling in extracellular environments. The growth factor (GF) domain common to all family members and many of their antagonists evolved from a common cystine knot growth factor (CKGF) domain. The CKGF superfamily comprises six distinct families in primitive metazoans, including the TGF-β and Dan families. Compared with Wnt/Frizzled and Notch/Delta families that also specify body axes, cell fate, tissues, and other families that contain CKGF domains that evolved in parallel, the TGF-β family was the most fruitful in evolution...
September 16, 2016: Cold Spring Harbor Perspectives in Biology
Martin Schlensog, Lara Magnus, Timon Heide, Julian Eschenbruch, Florian Steib, Maximilian Tator, Vera Kloten, Michael Rose, Erik Noetzel, Nadine T Gaisa, Ruth Knüchel, Edgar Dahl
Secreted frizzled related protein 3 (SFRP3) contains a cysteine-rich domain (CRD) that shares homology with Frizzled CRD and regulates WNT signaling. Independent studies showed epigenetic silencing of SFRP3 in melanoma and hepatocellular carcinoma. Moreover, a tumor suppressive function of SFRP3 was shown in androgen-independent prostate and gastric cancer cells. The current study is the first to investigate SFRP3 expression and its potential clinical impact on non-small cell lung carcinoma (NSCLC). WNT signaling components present on NSCLC subtypes were preliminary elucidated by expression data of The Cancer Genome Atlas (TCGA)...
September 13, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Huey Lin, Mia Angeli, Kwang Jin Chung, Chukwuemeka Ejimadu, Angelica Rivera Rosa, Techung Lee
Secreted Frizzled-related protein 2 (sFRP2) plays a key role in chronic fibrosis after myocardial infarction and in heart failure. The study was aimed at elucidating the mechanisms through which sFRP2 may regulate the growth and extracellular matrix (ECM) remodeling of adult mouse cardiac fibroblasts (CFs). We found that sFRP2 activates CFs in part through canonical Wnt/β-catenin signaling as evidenced by increased expression of Axin2 and Wnt3a, but not Wnt5a, as well as accumulation of nuclear β-catenin...
September 7, 2016: American Journal of Physiology. Cell Physiology
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
Marwa S Asem, Steven Buechler, Rebecca Burkhalter Wates, Daniel L Miller, M Sharon Stack
Wnt5a is involved in activating several non-canonical WNT signaling pathways, through binding to different members of the Frizzled- and Ror-family receptors. Wnt5a signaling is critical for regulating normal developmental processes, including proliferation, differentiation, migration, adhesion and polarity. However, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a in regulating cancer cell invasion, metastasis, metabolism and inflammation...
August 26, 2016: Cancers
Romain Désert, Sihem Mebarki, Mireille Desille, Marie Sicard, Elise Lavergne, Stéphanie Renaud, Damien Bergeat, Laurent Sulpice, Christine Perret, Bruno Turlin, Bruno Clément, Orlando Musso
Hepatocellular carcinoma (HCC) is the 3rd cause of cancer-related death worldwide. Most cases arise in a background of chronic inflammation, extracellular matrix (ECM) remodeling, severe fibrosis and stem/progenitor cell amplification. Although HCCs are soft cellular tumors, they may contain fibrous nests within the tumor mass. Thus, the aim of this study was to explore cancer cell phenotypes in fibrous nests. Combined anatomic pathology, tissue microarray and real-time PCR analyses revealed that HCCs (n=82) containing fibrous nests were poorly differentiated, expressed Wnt pathway components and target genes, as well as markers of stem/progenitor cells, such as CD44, LGR5 and SOX9...
August 18, 2016: International Journal of Biochemistry & Cell Biology
Yuyao Tian, Weiping Wang, Qin Lu, Ping Chen, Kangtao Ma, Zhuqing Jia, Chunyan Zhou
Signaling pathways play an important role in cardiogenesis. Secreted frizzled-related protein 4 (SFRP4), a member of the Wnt family, contributes to adipogenesis and tumorigenesis. However, how SFRP4 participates in cardiogenesis and the detailed molecular mechanisms involved have not been elucidated. The aim of this work was to determine cross-talk between SFRP4, integrin α1β1, and Notch1 during cardiac differentiation of P19CL6 cells. Using a well-established in vitro P19CL6 cell cardiomyocyte differentiation system, we found that SFRP4 inhibited P19CL6 cell cardiac differentiation via SFRP4 overexpression or knockdown...
November 2016: Cellular Signalling
Y-H Taguchi, Mitsuo Iwadate, Hideaki Umeyama
BACKGROUND: Non-small cell lung cancer (NSCLC) remains a lethal disease despite many proposed treatments. Recent studies have indicated that epigenetic therapy, which targets epigenetic effects, might be a new therapeutic methodology for NSCLC. However, it is not clear which objects (e.g., genes) this treatment specifically targets. Secreted frizzled-related proteins (SFRPs) are promising candidates for epigenetic therapy in many cancers, but there have been no reports of SFRPs targeted by epigenetic therapy for NSCLC...
2016: BMC Medical Genomics
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