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https://www.readbyqxmd.com/read/28737757/non-canonical-wnt-pcp-signalling-in-cancer-fzd6-takes-centre-stage
#1
REVIEW
G Corda, A Sala
Frizzled receptors are the mediators of the wnt canonical and non-canonical pathways, which play fundamental roles in cell differentiation and organism development. A large body of work indicates that dysregulation of wnt signalling is a feature of oncogenic transformation, but most of the studies published so far focus on the assessment of the consequences of aberrations of the canonical pathway in human cancer. In this review, we discuss the emerging role of the wnt non-canonical pathway regulated by frizzled receptor 6 (Fzd6) in the pathogenesis of different types of human malignancies...
July 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28736081/frizzled-7-mediates-tgf-%C3%AE-induced-pulmonary-fibrosis-by-transmitting-non-canonical-wnt-signaling
#2
Shuhong Guan, Jun Zhou
Pulmonary fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix. Both TGF-β and Wnt signaling have been implicated in the regulation of organ fibrosis. However little is known about whether TGF-β-induced gene expression changes in Wnt signaling pathway could predict disease progression. In the study, we investigated the interaction between TGF-β and Wnt signaling in mediating pulmonary fibrosis by big data analysis, in vitro and in vivo experimental studies and clinical data analysis...
July 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28733458/mapping-of-wnt-frizzled-interactions-by-multiplex-crispr-targeting-of-receptor-gene-families
#3
Oksana Voloshanenko, Philipp Gmach, Jan Winter, Dominique Kranz, Michael Boutros
Signaling pathway modules are often encoded by several closely related paralogous genes that can have redundant roles and are therefore difficult to analyze by loss-of-function analysis. A typical example is the Wnt signaling pathway, which in mammals is mediated by 19 Wnt ligands that can bind to 10 Frizzled (FZD) receptors. Although significant progress in understanding Wnt-FZD receptor interactions has been made in recent years, tools to generate systematic interaction maps have been largely lacking. Here we generated cell lines with multiplex mutant alleles of FZD1, FZD2, and FZD7 and demonstrate that these cells are unresponsive to canonical Wnt ligands...
July 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#4
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#5
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
July 18, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28709873/deregulation-of-wnt2-fzd3-%C3%AE-catenin-pathway-compromises-the-estrogen-synthesis-in-cumulus-cells-from-patients-with-polycystic-ovary-syndrome
#6
Gu-Yuan Qiao, Bing-Wei Dong, Chao-Juan Zhu, Chang-You Yan, Bi-Liang Chen
Mechanistic insight into estrogen deficiency by polycystic ovary syndrome (PCOS) remains a longstanding challenge in reproductive medicine. Recent advance suggest that Wingless-type MMTV integration site family members (WNTs), in concert with its Frizzled (FZD) receptors, regulate normal folliculogenesis, luteogenesis and ovarian steroidogenesis. However, no studies have so far investigated any causality between WNT-FZDs interactions and disrupted estrogen synthesis under certain pathological conditions. Here, we show that (i) FZD3 expression was significantly up-regulated in the cumulus cells (CCs) from PCOS patients...
July 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28708837/extracellular-inhibitors-can-attenuate-tumorigenic-wnt-pathway-activity-in-adenomatous-polyposis-coli-mutants-predictions-of-a-validated-mathematical-model
#7
Gili Hochman, Karin Halevi-Tobias, Yuri Kogan, Zvia Agur
BACKGROUND: Despite considerable investigational efforts, no method to overcome the pathogenesis caused by loss of function (LoF) mutations in tumor suppressor genes has been successfully translated to the clinic. The most frequent LoF mutation in human cancers is Adenomatous polyposis coli (APC), causing aberrant activation of the Wnt pathway. In nearly all colon cancer tumors, the APC protein is truncated, but still retains partial binding abilities. OBJECTIVE & METHODS: Here, we tested the hypothesis that extracellular inhibitors of the Wnt pathway, although acting upstream of the APC mutation, can restore normal levels of pathway activity in colon cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28686724/dipeptidyl-peptidase-4-inhibitor-gemigliptin-protects-against-vascular-calcification-in-an-experimental-chronic-kidney-disease-and-vascular-smooth-muscle-cells
#8
Soon-Youn Choi, Hye-Myung Ryu, Eun-Joo Oh, Ji-Young Choi, Jang-Hee Cho, Chan-Duck Kim, Yong-Lim Kim, Sun-Hee Park
Although dipeptidyl peptidase-4 inhibitors, a class of antidiabetic drugs, have various pleiotropic effects, it remains undetermined whether gemigliptin has a beneficial effect on vascular calcification. Therefore, this study was performed to evaluate the effect of gemigliptin on vascular calcification in a rat model of adenine-induced chronic kidney disease and in cultured vascular smooth muscle cells. Gemigliptin attenuated calcification of abdominal aorta and expression of RUNX2 in adenine-induced chronic kidney disease rats...
2017: PloS One
https://www.readbyqxmd.com/read/28678406/synovial-wnt-signaling-induces-the-expression-of-mmps-and-is-associated-with-disease-progression-in-early-symptomatic-osteoarthritis-patients
#9
Martijn H van den Bosch, Arjen B Blom, Fons A van de Loo, Marije I Koenders, Floris P Lafeber, Wim B van den Berg, Peter M van der Kraan, Peter L van Lent
OBJECTIVES: Increased Wnt signaling in chondrocytes is associated with osteoarthritis development. However, osteoarthritis is considered a disease of the entire joint, where the synovium has been attributed an important role in the development of joint pathology. Here, we determined whether Wnt signaling in the synovial tissue could contribute to osteoarthritis pathology through the production of MMPs. Furthermore, we determined the relation of synovial expression of Frizzled (FZD) receptors and the Wnt inhibitor FRZB to MMP expression and disease progression in early osteoarthritis patients (CHECK cohort)...
July 5, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28675177/norrin-induced-frizzled4-endocytosis-and-endo-lysosomal-trafficking-control-retinal-angiogenesis-and-barrier-function
#10
Chi Zhang, Maria B Lai, Lavan Khandan, Lindsey A Lee, Zhe Chen, Harald J Junge
Angiogenesis and blood-brain barrier formation are required for normal central nervous system (CNS) function. Both processes are controlled by Wnt or Norrin (NDP) ligands, Frizzled (FZD) receptors, and β-catenin-dependent signalling in vascular endothelial cells. In the retina, FZD4 and the ligand NDP are critical mediators of signalling and are mutated in familial exudative vitreoretinopathy. Here, we report that NDP is a potent trigger of FZD4 ubiquitination and induces internalization of the NDP receptor complex into the endo-lysosomal compartment...
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28671046/let7b-modulates-the-wnt-%C3%AE-catenin-pathway-in-liver-cancer-cells-via-downregulated-frizzled4
#11
Hui Cai, Yifeng Chen, Xiaojun Yang, Shixun Ma, Qi Wang, Yupeng Zhang, Xiangdong Niu, Guogan Ding, Yuan Yuan
Let7 microRNA implicated in many cellular processes and participated in the progress of various tumors. Similarly, Wnt signaling pathway plays an important role in morphogenesis, differentiation, cell survival, and proliferation. However, there is little research focusing on the relevance between Let7b and Wnt/β-catenin signaling pathway, especially in liver cancer cell. To study this, human liver cancer cells HUH7 and MHCC97H were cultured, enhanced, or inhibited the expression of Let7b in two cell lines...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28669726/knockdown-of-frizzled-7-inhibits-cell-growth-and-metastasis-and-promotes-chemosensitivity-of-esophageal-squamous-cell-carcinoma-cells-by-inhibiting-wnt-signaling
#12
Xiaoping Liu, Yanli Yan, Weiping Ma, Suge Wu
A growing body of evidence suggests that frizzled-7 (FZD7) is an important oncogene in multiple human malignancies and is involved in regulating sensitivity to chemotherapeutic drugs. However, little is known about the expression and function of FZD7 in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the functional significance of FZD7 in ESCC. Here, we found that both mRNA and protein expression levels of FZD7 were highly upregulated in ESCC cell lines. The knockdown of FZD7 inhibited cell growth, induced cell apoptosis, and suppressed cell migration and invasion of ESCC cells in vitro...
June 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28668722/the-tyrosine-y250-2-39-in-frizzled-4-defines-a-conserved-motif-important-for-structural-integrity-of-the-receptor-and-recruitment-of-disheveled
#13
Katerina Strakova, Pierre Matricon, Chika Yokota, Elisa Arthofer, Ondrej Bernatik, David Rodriguez, Ernest Arenas, Jens Carlsson, Vitezslav Bryja, Gunnar Schulte
Frizzleds (FZDs) are unconventional G protein-coupled receptors, which activate diverse intracellular signaling pathways via the phosphoprotein Disheveled (DVL) and heterotrimeric G proteins. The interaction interplay of FZDs with DVL and G proteins is complex, involves different regions of FZD and the potential dynamics are poorly understood. In the present study, we aimed to characterize the function of a highly conserved tyrosine (Y250(2.39)) in the intracellular loop 1 (IL1) of human FZD4. We have found Y250(2...
June 29, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28635355/aberrant-wnt-signaling-a-special-focus-in-cns-diseases
#14
Mercedes Arnés, Sergio Casas Tintó
Wnt signals regulate cell proliferation, migration and differentiation during development, as well as synaptic transmission and plasticity in the adult brain. Abnormal Wnt signaling is central to a number of brain pathologies. We review here, the significance of this pathway focused in the contribution of the most frequent alterations in receptors, secretable modulators and downstream targets in Alzheimer's disease (AD) and Glioblastoma (GBM). β-catenin and GSK3 levels are pivotal in the neurodegeneration associated to AD contributing to memory deficits, tau phosphorylation, increased β-amyloid production and modulation of Apolipoprotein E in the brain...
June 21, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28622009/mir-139-5p-represses-bmsc-osteogenesis-via-targeting-wnt-%C3%AE-catenin-signaling-pathway
#15
Haitao Long, Buhua Sun, Liang Cheng, Shushan Zhao, Yong Zhu, Ruibo Zhao, Jianxi Zhu
Osteogenesis of mesenchymal stem cells (MSCs) has played a necessary role in the repair of bone. According to some reports, microRNAs participate in different physiological activity of the cells, including cell differentiation. This study investigated the function that miR-139-5p plays in the osteogenic differentiation of human bone marrow MSCs (hBMSCs). In addition to miR-139-5p, the effects of alkaline phosphatase (ALP), a membrane-bound metalloenzyme that is considered an early osteogenic differentiation marker, have also been investigated...
June 16, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28614361/molecular-cloning-characterization-and-expression-analysis-of-frizzled-6-in-the-small-intestine-of-pigs-sus-scrofa
#16
Lijun Zou, Xiaocheng Wang, Liping Jiang, Shengping Wang, Xia Xiong, Huansheng Yang, Wei Gao, Min Gong, Chien-An A Hu, Yulong Yin
Frizzled 6 (FZD6) encodes an integral membrane protein that functions in multiple signal transduction pathways, for example, as a receptor in Wnt/planar cell polarity (PCP) signaling pathway for polarized cell migration and organ morphogenesis. Mutations in FZD6 have been identified in a variety of tumors. In this study, the full-length cDNA of Sus scrofa FZD6 (Sfz6) was cloned and characterized. Nucleotide sequence analysis demonstrates that the Sfz6 gene encodes the 712 amino-acid (aa) protein with seven transmembrane domain...
2017: PloS One
https://www.readbyqxmd.com/read/28605875/mir-1254-promotes-lung-cancer-cell-proliferation-by-targeting-sfrp1
#17
Hong Li, Tian Yang, Dong Shang, Zhongmin Sun
Lung cancer is the leading cause of cancer deaths worldwide, many miRNAs play critical role in lung cancer initiation and progression. Here, we demonstrated that miR-1254 was upregulated in lung cancer tissues and cells. miR-1254 overexpression promoted lung cancer cell proliferation determined by MTT assay, colony formation assay, soft agar growth ability assay and BrdU incorporation assay, miR-1254 knockdown suppressed lung cancer cell proliferation. Mechanism analysis revealed that Wnt/β-catenin pathway antagonist secreted frizzled related protein 1 (SFRP1) was its target, its expression was opposite to SFRP1 level, and directly bound to the 3'UTR of SFRP1...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28596769/c1-complex-an-adaptable-proteolytic-module-for-complement-and-non-complement-functions
#18
REVIEW
Jinhua Lu, Uday Kishore
Complement C1 is the defining component of the classical pathway. Within the C1qC1r2C1s2 complex, C1q functions as a molecular scaffold for C1r2C1s2 and C1q binding to its ligands activates these two serine proteases. The classic C1q ligands are antigen-bound antibodies and activated C1s cleaves C4 and C2 to initiate the complement cascade. Recent studies suggest broad C1 functions beyond the complement system. C1q binds to the Frizzled receptors to activate C1s, which cleaves lipoprotein receptor-related protein 6 to trigger aging-associated Wnt receptor signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28589318/matricellular-proteins-in-cancer-a-focus-on-secreted-frizzled-related-proteins
#19
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/28576860/coordination-of-heparan-sulfate-proteoglycans-with-wnt-signaling-to-control-cellular-migrations-and-positioning-in-caenorhabditis-elegans
#20
Kristian Saied-Santiago, Robert A Townley, John D Attonito, Dayse S da Cunha, Carlos A Diaz-Balzac, Eillen Tecle, Hannes E Bülow
Heparan sulfates are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as co-factors for multiple signaling pathways, including the Wnt signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts...
June 2, 2017: Genetics
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