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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/28736504/pleomorphism-and-drug-resistant-cancer-stem-cells-are-characteristic-of-aggressive-primary-meningioma-cell-lines
#2
Ishaq Khan, Saleh Baeesa, Mohammed Bangash, Hans-Juergen Schulten, Fahad Alghamdi, Hanadi Qashqari, Nawal Madkhali, Angel Carracedo, Mohamad Saka, Awatif Jamal, Jaudah Al-Maghrabi, Mohammed AlQahtani, Saleh Al-Karim, Ghazi Damanhouri, Kulvinder Saini, Adeel Chaudhary, Adel Abuzenadah, Deema Hussein
BACKGROUND: Meningioma tumors arise in arachnoid membranes, and are the most reported central nervous system (CNS) tumors worldwide. Up to 20% of grade I meningioma tumors reoccur and currently predictive cancer stem cells (CSCs) markers for aggressive and drug resistant meningiomas are scarce. METHODS: Meningioma tissues and primary cell lines were investigated using whole transcriptome microarray analysis, immunofluorescence staining of CSCs markers (including CD133, Sox2, Nestin, and Frizzled 9), and drug treatment with cisplatin or etoposide...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28736081/frizzled-7-mediates-tgf-%C3%AE-induced-pulmonary-fibrosis-by-transmitting-non-canonical-wnt-signaling
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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/28694840/hepatic-adipocyte-enteric-and-pancreatic-hormones-response-to-dietary-macronutrient-composition-and-relationship-with-metabolism
#9
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/28687085/regulation-of-early-growth-response-2-expression-by-secreted-frizzled-related-protein-1
#10
Kelly J Gregory, Stephanie M Morin, Sallie S Schneider
BACKGROUND: Secreted frizzled-related protein 1 (SFRP1) expression is down-regulated in a multitude of cancers, including breast cancer. Loss of Sfrp1 also exacerbates weight gain as well as inflammation. Additionally, loss of SFRP1 enhances TGF-β signaling and the downstream MAPK pathway. TGF-β has been shown to increase the expression of Early Growth Response 2 (EGR2), a transcription factor implicated in immune function in a wide variety of cell types. The work described here was initiated to determine whether SFRP1 modulation affects TGF-β mediated EGR2 expression in mammary tissues as well as macrophage polarization...
July 7, 2017: BMC Cancer
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
#11
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/28681272/comparative-rna-sequencing-analysis-of-er-based-hsp90-functions-and-signal-pathways-in-tribolium-castaneum
#12
Wenfeng Xiong, Mengfan Zhai, Xiaojuan Yu, Luting Wei, Jinjuan Mao, Juanjuan Liu, Jia Xie, Bin Li
Tribolium castaneum, the red flour beetle, is a major agriculture pest that damages stored grains and cereal products. Heat-shock protein 90 of T. castaneum (Tchsp90) has been reported to play pivotal roles in heat stress response, development, reproduction, and life span. However, the signaling pathway of Tchsp90 remains unclear. Thus, the global transcriptome profiles between RNA interference (RNAi)-treated insects (ds-Tchsp90) and control insects of T. castaneum were investigated and compared by RNA sequencing...
July 5, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28680582/estrogen-receptor-dependent-attenuation-of-hypoxia-induced-changes-in-the-lung-genome-of-pulmonary-hypertension-rats
#13
Andrea L Frump, Marjorie E Albrecht, Jeanette N McClintick, Tim Lahm
17β-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis in the hypoxic lung, we performed a microarray analysis in lungs from HPH rats treated with E2 (75 mcg/kg/day) ± ER-antagonist ICI182,780 (3 mg/kg/day). Untreated HPH rats and normoxic rats served as controls...
March 2017: Pulmonary Circulation
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
#14
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
#15
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
#16
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
#17
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
#18
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/28665270/meru-couples-planar-cell-polarity-with-apical-basal-polarity-during-asymmetric-cell-division
#19
Jennifer J Banerjee, Birgit L Aerne, Maxine V Holder, Simon Hauri, Matthias Gstaiger, Nicolas Tapon
Polarity is a shared feature of most cells. In epithelia, apical-basal polarity often coexists, and sometimes intersects with planar cell polarity (PCP), which orients cells in the epithelial plane. From a limited set of core building blocks (e.g. the Par complexes for apical-basal polarity and the Frizzled/Dishevelled complex for PCP), a diverse array of polarized cells and tissues are generated. This suggests the existence of little-studied tissue-specific factors that rewire the core polarity modules to the appropriate conformation...
June 30, 2017: ELife
https://www.readbyqxmd.com/read/28658627/tspan12-is-a-norrin-co-receptor-that-amplifies-frizzled4-ligand-selectivity-and-signaling
#20
Maria B Lai, Chi Zhang, Jianli Shi, Verity Johnson, Lavan Khandan, John McVey, Michael W Klymkowsky, Zhe Chen, Harald J Junge
Accessory proteins in Frizzled (FZD) receptor complexes are thought to determine ligand selectivity and signaling amplitude. Genetic evidence indicates that specific combinations of accessory proteins and ligands mediate vascular β-catenin signaling in different CNS structures. In the retina, the tetraspanin TSPAN12 and the ligand norrin (NDP) mediate angiogenesis, and both genes are linked to familial exudative vitreoretinopathy (FEVR), yet the molecular function of TSPAN12 remains poorly understood. Here, we report that TSPAN12 is an essential component of the NDP receptor complex and interacts with FZD4 and NDP via its extracellular loops, consistent with an action as co-receptor that enhances FZD4 ligand selectivity for NDP...
June 27, 2017: Cell Reports
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