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https://www.readbyqxmd.com/read/28069946/wnt5a-is-essential-for-hippocampal-dendritic-maintenance-and-spatial-learning-and-memory-in-adult-mice
#1
Chih-Ming Chen, Lauren L Orefice, Shu-Ling Chiu, Tara A LeGates, Samer Hattar, Richard L Huganir, Haiqing Zhao, Baoji Xu, Rejji Kuruvilla
Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28057866/evidence-for-opposing-roles-of-celsr3-and-vangl2-in-glutamatergic-synapse-formation
#2
Sonal Thakar, Liqing Wang, Ting Yu, Mao Ye, Keisuke Onishi, John Scott, Jiaxuan Qi, Catarina Fernandes, Xuemei Han, John R Yates, Darwin K Berg, Yimin Zou
The signaling mechanisms that choreograph the assembly of the highly asymmetric pre- and postsynaptic structures are still poorly defined. Using synaptosome fractionation, immunostaining, and coimmunoprecipitation, we found that Celsr3 and Vangl2, core components of the planar cell polarity (PCP) pathway, are localized at developing glutamatergic synapses and interact with key synaptic proteins. Pyramidal neurons from the hippocampus of Celsr3 knockout mice exhibit loss of ∼50% of glutamatergic synapses, but not inhibitory synapses, in culture...
January 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28051879/wnt5a-promoter-methylation-is-associated-with-better-responses-and-longer-progression-free-survival-in-colorectal-cancer-patients-treated-with-5-fluorouracil-based-chemotherapy
#3
Guozhong Jiang, Jiangxin Lin, Weiwei Wang, Miaomiao Sun, Kuisheng Chen, Feng Wang
BACKGROUND: Aberrant activation of the canonical WNT or WNT/β-catenin signaling pathway plays a pivotal role in multiple types of cancers. WNT5A, a nontransforming WNT protein suppressing the Wnt/β-catenin signaling pathway, is frequently detected to be hypermethylated in colorectal cancer (CRC). In this study, we investigated the prognostic value of WNT5A methylation in human patients and its potential underlying molecular mechanisms in cultured human CRC cells. METHODS: We measured WNT5A mRNA level using qRT-PCR and DNA methylation using methylation-specific PCR (MSP) in HCT116, HT29, SW620, HCT8, LoVo, SW480, and Rko CRC cells...
January 4, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28042326/exosomes-derived-from-mir-140-5p-overexpressing-human-synovial-mesenchymal-stem-cells-enhance-cartilage-tissue-regeneration-and-prevent-osteoarthritis-of-the-knee-in-a-rat-model
#4
Shi-Cong Tao, Ting Yuan, Yue-Lei Zhang, Wen-Jing Yin, Shang-Chun Guo, Chang-Qing Zhang
OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p...
2017: Theranostics
https://www.readbyqxmd.com/read/28030815/a-novel-non-canonical-wnt-signature-for-prostate-cancer-aggressiveness
#5
Elise Sandsmark, Ailin Falkmo Hansen, Kirsten M Selnæs, Helena Bertilsson, Anna M Bofin, Alan J Wright, Trond Viset, Elin Richardsen, Finn Drabløs, Tone F Bathen, May-Britt Tessem, Morten B Rye
Activation of the Canonical Wnt pathway (CWP) has been linked to advanced and metastatic prostate cancer, whereas the Wnt5a-induced non-canonical Wnt pathway (NCWP) has been associated with both good and poor prognosis. A newly discovered NCWP, Wnt5/Fzd2, has been shown to induce epithelial-to-mesenchymal transition (EMT) in cancers, but has not been investigated in prostate cancer. The aim of this study was to investigate if the CWP and NCWP, in combination with EMT, are associated with metabolic alterations, aggressive disease and biochemical recurrence in prostate cancer...
December 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/28011620/wnt5a-drives-an-invasive-phenotype-in-human-glioblastoma-stem-like-cells
#6
Elena Binda, Alberto Visioli, Fabrizio Giani, Nadia Trivieri, Orazio Palumbo, Silvia Restelli, Fabio Dezi, Tommaso Mazza, Caterina Fusilli, Federico Legnani, Massimo Carella, Francesco DiMeco, Rohit Duggal, Angelo Luigi Vescovi
Brain invasion by glioblastoma (hGBM) determines prognosis, recurrence and lethality in patients, but no master factor coordinating the invasive properties of GBM has been identified. Here we report evidence favouring such a role for the non-canonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal GBM from poorly motile proneural and classical GBM. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly-infiltrating mesenchymal GBM cells (Wnt5aHigh)...
December 23, 2016: Cancer Research
https://www.readbyqxmd.com/read/28005837/multiple-roles-of-wnt5a-in-breast-cancer
#7
Ruolan Zeng, Junhui Huang, Mei-Zuo Zhong, Li Li, Guorong Yang, Li Liu, Yin Wu, Xiaoyi Yao, Jing Shi, Zhifu Wu
Breast cancer is one of the most common malignant tumors of women. Modern combinatorial therapeutic regimens can reduce patient tumor burdens to undetectable levels, yet in many cases these tumors will relapse. Understanding of breast cancer biology, developing more potent therapeutic approaches, and overcoming resistance are of great importance. WNT5A is a non-canonical signaling member of the WNT family. Its role in breast cancer still remains unclear. Most of the evidence shows that WNT5A is a suppressor in breast cancer and loss of its expression is associated with poor prognosis, while some evidence suggests the tumorigenicity of WNT5A...
December 22, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28004111/col11a1-is-overexpressed-in-gastric-cancer-tissues-and-regulates-proliferation-migration-and-invasion-of-hgc-27-gastric-cancer-cells-in%C3%A2-vitro
#8
Aiqing Li, Jun Li, Jinping Lin, Wei Zhuo, Jianmin Si
The role of COL11A1 in carcinogenesis is increasingly recognized. However, the biological role and potential mechanisms of COL11A1 in gastric cancer have not been elucidated. In the present study, the COL11A1 mRNA expression in 57 patients with gastric cancer was measured by reverse transcription quantitative PCR (RT-qPCR), and the biological effects of COL11A1 suppression were determined using MTS, monolayer colony formation, flow cytometry and Transwell assays. In addition, the potential molecular mechanisms of COL11A1 in gastric cancer were analyzed by western blotting and cDNA microarray analysis...
January 2017: Oncology Reports
https://www.readbyqxmd.com/read/27998927/niche-wnt5a-regulates-the-actin-cytoskeleton-during-regeneration-of-hematopoietic-stem-cells
#9
Christina Schreck, Rouzanna Istvánffy, Christoph Ziegenhain, Theresa Sippenauer, Franziska Ruf, Lynette Henkel, Florian Gärtner, Beate Vieth, M Carolina Florian, Nicole Mende, Anna Taubenberger, Áine Prendergast, Alina Wagner, Charlotta Pagel, Sandra Grziwok, Katharina S Götze, Jochen Guck, Douglas C Dean, Steffen Massberg, Marieke Essers, Claudia Waskow, Hartmut Geiger, Mathias Schiemann, Christian Peschel, Wolfgang Enard, Robert A J Oostendorp
Here, we show that the Wnt5a-haploinsufficient niche regenerates dysfunctional HSCs, which do not successfully engraft in secondary recipients. RNA sequencing of the regenerated donor Lin(-) SCA-1(+) KIT(+) (LSK) cells shows dysregulated expression of ZEB1-associated genes involved in the small GTPase-dependent actin polymerization pathway. Misexpression of DOCK2, WAVE2, and activation of CDC42 results in apolar F-actin localization, leading to defects in adhesion, migration and homing of HSCs regenerated in a Wnt5a-haploinsufficient microenvironment...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27965056/porcupine-dependent-wnt-signaling-controls-stromal-proliferation-and-endometrial-gland-maintenance-through-the-action-of-distinct-wnts
#10
Omar Farah, Steffen Biechele, Janet Rossant, Daniel Dufort
Wnt signaling has been shown to be important in orchestrating proper development of the female reproductive tract. In the uterus, six members of the Wnt family are expressed in the neonatal endometrium and deletion of individual Wnt genes often leads to similar phenotypes, suggesting an interaction of these genes in uterine development and function. Furthermore, Wnts may have complementary functions, which could mask the identification of their individual functional role in single gene deletions. To circumvent this issue, we have generated a deletion of the Porcupine homolog within the female reproductive tract using progesterone receptor-Cre mice (Pgr(Cre/+)); preventing Wnt secretion from the producing cells...
December 10, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27959384/pro-metastatic-intracellular-signaling-of-the-elaidic-trans-fatty-acid
#11
Kiyomu Fujii, Yi Luo, Rina Fujiwara-Tani, Shingo Kishi, Song He, Shuyun Yang, Takamitsu Sasaki, Hitoshi Ohmori, Hiroki Kuniyasu
Trans fatty acids (TFAs) are risk factors of cardiovascular disorders, and a few studies have reported the cancer-promoting effects of TFAs. In the present study, we examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA increased the metastasis of CT26 mouse CRC cells by inducing the expression of stemness markers nucleostemin (NS) and CD133. Mechanisms underlying EA-induced signaling were confirmed by determining the binding of EA to G-protein coupled receptor 40 (GPR40) and GPR120 by performing surface protein internalization assay...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27932350/role-of-noncanonical-wnts-signaling-pathway-in-human-aortic-valve-calcification
#12
Isabella Albanese, Bin Yu, Hamood Al-Kindi, Bianca Barratt, Leah Ott, Mohammad Al-Refai, Benoit de Varennes, Dominique Shum-Tim, Marta Cerruti, Ophélie Gourgas, Eric Rhéaume, Jean-Claude Tardif, Adel Schwertani
OBJECTIVE: The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification. APPROACH AND RESULTS: Using immunohistochemistry, RT-PCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs)...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27927230/molecular-control-of-nitric-oxide-synthesis-through-enos-and-caveolin-1-interaction-regulates-osteogenic-differentiation-of-adipose-derived-stem-cells-by-modulation-of-wnt-%C3%AE-catenin-signaling
#13
Nadeeka Bandara, Saliya Gurusinghe, Shiang Yong Lim, Haying Chen, Shuangfeng Chen, Dawei Wang, Bryan Hilbert, Le-Xin Wang, Padraig Strappe
BACKGROUND: Nitric oxide (NO) plays a role in a number of physiological processes including stem cell differentiation and osteogenesis. Endothelial nitric oxide synthase (eNOS), one of three NO-producing enzymes, is located in a close conformation with the caveolin-1 (CAV-1(WT)) membrane protein which is inhibitory to NO production. Modification of this interaction through mutation of the caveolin scaffold domain can increase NO release. In this study, we genetically modified equine adipose-derived stem cells (eASCs) with eNOS, CAV-1(WT), and a CAV-1(F92A) (CAV-1(WT) mutant) and assessed NO-mediated osteogenic differentiation and the relationship with the Wnt signaling pathway...
December 7, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27923152/hydronephrosis-in-the-wnt5a-ablated-kidney-is-caused-by-an-abnormal-ureter-bladder-connection
#14
Kangsun Yun, Alan O Perantoni
The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme...
December 3, 2016: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/27916087/-the-regulatory-role-of-wnt-signaling-pathway-in-the-proliferation-and-activation-of-memory-t-cells
#15
Lei Luo, Guangheng Luo, Qian Fang, Shan Huang, Hui Chen
Objective To study the regulatory effect of Wnt signaling pathway on the activation and proliferation of memory T cells (TMs). Methods We established the mouse model of skin allograft transplantation (BALB/c-C57BL/6), and then we sorted and cultured immature dendritic cells (imDCs), mature dendritic cells (mDCs) and TMs from the C57BL/6 mice by immunomagnetic bead cell sorting. The imDCs or mDCs loading antigens from BALB/c mice were co-cultured with TMs in a 96-well plate or Transwell(TM) plate (MLR). The (3)H-TdR was used to detect the proliferation of TMs...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27913393/epigenetically-activated-wnt5a-promotes-glioblastoma-progression
#16
(no author information available yet)
WNT5A signaling drives an endothelial cell transcriptional program in GBM stem cells.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27904138/cirmtuzumab-inhibits-wnt5a-induced-rac1-activation-in-chronic-lymphocytic-leukemia-treated-with-ibrutinib
#17
J Yu, L Chen, B Cui, Christina Wu, M Y Choi, Y Chen, L Zhang, L Z Rassenti, G F Widhopf Ii, T J Kipps
Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27895670/wnt5a-increases-properties-of-lung-cancer-stem-cells-and-resistance-to-cisplatin-through-activation-of-wnt5a-pkc-signaling-pathway
#18
Jiali Yang, Kangjian Zhang, Jing Wu, Juan Shi, Jing Xue, Jing Li, Juan Chen, Yongzhao Zhu, Jun Wei, Jinxi He, Xiaoming Liu
The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27895173/human-regulatory-t-cells-mediate-transcriptional-modulation-of-dendritic-cell-function
#19
Emily Mavin, Lindsay Nicholson, Syed Rafez Ahmed, Fei Gao, Anne Dickinson, Xiao-Nong Wang
Regulatory T cells (Treg) attenuate dendritic cell (DC) maturation and stimulatory function. Current knowledge on the functional impact of semimature DC is limited to CD4(+) T cell proliferation and cytokine production. Little is known about the molecular basis underpinning the functional effects of Treg-treated DC (Treg-DC). We present novel evidence that Treg-DC skewed CD4(+) naive T cell polarization toward a regulatory phenotype and impaired CD8(+) T cell allo-reactive responses, including their ability to induce target tissue damage in a unique in vitro human graft-versus-host disease skin explant model...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895148/trpc5-regulates-differentiation-through-the-ca2-wnt5a-signal-pathway-in-colorectal-cancer
#20
Zhen Chen, Chunlei Tang, Yaodan Zhu, Mingxu Xie, Dongxu He, Qiongxi Pan, Peng Zhang, Dong Hua, Teng Wang, Linfang Jin, Xiaowei Qi, Yifei Zhu, Xiaoqiang Yao, Jian Jin, Xin Ma
Transient receptor potential channel 5 (TrpC5) is member of the TrpC subgroup, and it forms a receptor-activated non-selective Ca(2+) channel. The architecture of the TrpC5 channel is poorly understood. Here, we report that TrpC5 is a key factor in regulating differentiation in colorectal cancer. Through a study of specimens from a large cohort of patients with colorectal cancer, we found that TrpC5 was highly expressed and its cellular level correlated with tumor grade. We further showed that up-regulated TrpC5 caused a robust [Ca(2+)]i rise, increased Wnt5a expression, and the nuclear translocation of β-catenin, leading to a reduction of cancer differentiation and an increase of cancer cell stemness...
November 28, 2016: Clinical Science (1979-)
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