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https://www.readbyqxmd.com/read/28916833/inhibition-of-wnt-%C3%AE-catenin-pathway-and-histone-acetyltransferase-activity-by-rimonabant-a-therapeutic-target-for-colon-cancer
#1
Maria Chiara Proto, Donatella Fiore, Chiara Piscopo, Silvia Franceschelli, Valentina Bizzarro, Chiara Laezza, Gianluigi Lauro, Alessandra Feoli, Alessandra Tosco, Giuseppe Bifulco, Gianluca Sbardella, Maurizio Bifulco, Patrizia Gazzerro
In a high percentage (≥85%) of both sporadic and familial adenomatous polyposis forms of colorectal cancer (CRC), the inactivation of the APC tumor suppressor gene initiates tumor formation and modulates the Wnt/β-Catenin transduction pathways involved in the control of cell proliferation, adhesion and metastasis. Increasing evidence showed that the endocannabinoids control tumor growth and progression, both in vitro and in vivo. We evaluated the effect of Rimonabant, a Cannabinoid Receptor 1 (CB1) inverse agonist, on the Wnt/β-Catenin pathway in HCT116 and SW48 cell lines carrying the genetic profile of metastatic CRC poorly responsive to chemotherapies...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916299/non-canonical-wnt-mediated-neurogenic-differentiation-of-human-bone-marrow-derived-mesenchymal-stem-cells
#2
Sujeong Jang, Hyong-Ho Cho, Jong-Seong Park, Han-Seong Jeong
Bone marrow-derived mesenchymal stem cells (BM-MSCs), which are characterized by multipotency and self-renewal, are responsible for tissue regeneration and repair. We have previously reported in adipose tissue-derived MSCs that only Wnt5a is enhanced at neurogenic differentiation, and the mechanism of differentiation is dependent on the Wnt5a/JNK pathway; however, the role of Wnt/MAPK pathway is yet to be investigated in neurogenic differentiation in BM-MSCs. We compared the transcriptional expression of Wnt in neurogenic induced-hBM-MSCs (NI-hBM-MSCs) with that in primary hBM-MSCs, using RT-PCR, qPCR, and western blotting...
September 12, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28887323/atg5-mediates-a-positive-feedback-loop-between-wnt-signaling-and-autophagy-in-melanoma
#3
Abibatou Ndoye, Anna Budina-Kolomets, Curtis H Kugel, Marie R Webster, Amanpreet Kaur, Reeti Behera, Vito W Rebecca, Ling Li, Patricia A Brafford, Qin Liu, Y N Vashisht Gopal, Michael A Davies, Gordon B Mills, Xiaowei Xu, Hong Wu, Meenhard Herlyn, Michael C Nicastri, Jeffrey D Winkler, Maria S Soengas, Ravi K Amaravadi, Maureen E Murphy, Ashani T Weeraratna
Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin...
September 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28886116/treatment-with-the-wnt5a-mimicking-peptide-foxy-5-effectively-reduces-the-metastatic-spread-of-wnt5a-low-prostate-cancer-cells-in-an-orthotopic-mouse-model
#4
Giacomo Canesin, Susan Evans-Axelsson, Rebecka Hellsten, Agnieszka Krzyzanowska, Chandra P Prasad, Anders Bjartell, Tommy Andersson
Prostate cancer patients with high WNT5A expression in their tumors have been shown to have more favorable prognosis than those with low WNT5A expression. This suggests that reconstitution of Wnt5a in low WNT5A-expressing tumors might be an attractive therapeutic approach. To explore this idea, we have in the present study used Foxy-5, a WNT5A mimicking peptide, to investigate its impact on primary tumor and metastasis in vivo and on prostate cancer cell viability, apoptosis and invasion in vitro. We used an in vivo orthotopic xenograft mouse model with metastatic luciferase-labeled WNT5A-low DU145 cells and metastatic luciferase-labeled WNT5A-high PC3prostate cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28885975/kinesin-superfamily-protein-kif26b-links-wnt5a-ror-signaling-to-the-control-of-cell-and-tissue-behaviors-in-vertebrates
#5
Michael W Susman, Edith P Karuna, Ryan C Kunz, Taranjit S Gujral, Andrea V Cantú, Shannon S Choi, Brigette Y Jong, Kyoko Okada, Michael K Scales, Jennie Hum, Linda S Hu, Marc W Kirschner, Ryuichi Nishinakamura, Soichiro Yamada, Diana J Laird, Li-En Jao, Steven P Gygi, Michael E Greenberg, Hsin-Yi Henry Ho
Wnt5a-Ror signaling constitutes a developmental pathway crucial for embryonic tissue morphogenesis, reproduction and adult tissue regeneration, yet the molecular mechanisms by which the Wnt5a-Ror pathway mediates these processes are largely unknown. Using a proteomic screen, we identify the kinesin superfamily protein Kif26b as a downstream target of the Wnt5a-Ror pathway. Wnt5a-Ror, through a process independent of the canonical Wnt/β-catenin-dependent pathway, regulates the cellular stability of Kif26b by inducing its degradation via the ubiquitin-proteasome system...
September 8, 2017: ELife
https://www.readbyqxmd.com/read/28880717/bivalent-histone-codes-on-wnt5a-during-odontogenic-differentiation
#6
Y Zhou, L Zheng, F Li, M Wan, Y Fan, X Zhou, W Du, C Pi, D Cui, B Zhang, J Sun, X Zhou
Lineage-committed differentiation is an essential biological program during odontogenesis, which is tightly regulated by lineage-specific genes. Some of these genes are modified by colocalization of H3K4me3 and H3K27me3 marks at promoter regions in progenitors. These modifications, named "bivalent domains," maintain genes in a poised state and then resolve for later activation or repression during differentiation. Wnt5a has been reported to promote odontogenic differentiation in dental mesenchyme. However, relatively little is known about the epigenetic modulations on Wnt5a activation during tooth development...
September 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28870803/suppression-of-wnt5a-but-not-wnts-relieves-chronic-post-thoracotomy-pain-via-anti-inflammatory-modulation-in-rats
#7
Afang Zhu, Le Shen, Li Xu, Weiyun Chen, Yuguang Huang
With regard to post-surgical pain, the incidence of chronic post-thoracotomy pain (CPTP) is second only to that caused by amputation and the underlying mechanism remains elusive. The emerging role of Wnts has been confirmed in the pathogenesis of neuropathic and inflammatory pain, both of which are known components of CPTP. We investigated whether Wnt3a and Wnt5a were involved in the development of CPTP, concerning their regulation of inflammatory responses in a previously established rat model. We observed up regulated protein levels of Wnt3a, Wnt5a, β-catenin, and TLR4, along with activated astrocytes and pro-inflammatory cytokines, in both dorsal root ganglia and the spinal cord dorsal horn...
September 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28864021/the-core-transcriptome-of-mammalian-placentas-and-the-divergence-of-expression-with-placental-shape
#8
Don L Armstrong, Michael R McGowen, Amy Weckle, Priyadarshini Pantham, Jason Caravas, Dalen Agnew, Kurt Benirschke, Sue Savage-Rumbaugh, Eviatar Nevo, Chong J Kim, Günter P Wagner, Roberto Romero, Derek E Wildman
INTRODUCTION: The placenta is arguably the most anatomically variable organ in mammals even though its primary function is conserved. METHOD: Using RNA-Seq, we measured the expression profiles of 55 term placentas of 14 species of mammals representing all major eutherian superordinal clades and marsupials, and compared the evolution of expression across clades. RESULTS: We identified a set of 115 core genes which is expressed (FPKM ≥10) in all eutherian placentas, including genes with immune-modulating properties (ANXA2, ANXA1, S100A11, S100A10, and LGALS1), cell-cell interactions (LAMC1, LUM, and LGALS1), invasion (GRB2 and RALB) and syncytialization (ANXA5 and ANXA1)...
September 2017: Placenta
https://www.readbyqxmd.com/read/28859077/distinct-roles-and-differential-expression-levels-of-wnt5a-mrna-isoforms-in-colorectal-cancer-cells
#9
Tsui-Chin Huang, Pin-Tse Lee, Ming-Heng Wu, Chi-Chen Huang, Chiung-Yuan Ko, Yi-Chao Lee, Ding-Yen Lin, Ya-Wen Cheng, Kuen-Haur Lee
The canonical Wnt/β-catenin pathway is constitutively activated in more than 90% of colorectal cancer (CRC) cases in which β-catenin contributes to CRC cell growth and survival. In contrast to the Wnt/β-catenin pathway, the non-canonical Wnt pathway can antagonize functions of the canonical Wnt/β-catenin pathway. Wnt5a is a key factor in the non-canonical Wnt pathway, and it plays diverse roles in different types of cancers. It was shown that reintroducing Wnt5a into CRC cells resulted in inhibited cell proliferation and impaired cell motility...
2017: PloS One
https://www.readbyqxmd.com/read/28857158/promoter-hypermethylation-in-plasma-derived-cell-free-dna-as-a-prognostic-marker-for-pancreatic-adenocarcinoma-staging
#10
Stine Dam Henriksen, Poul Henning Madsen, Anders Christian Larsen, Martin Berg Johansen, Inge Søkilde Pedersen, Henrik Krarup, Ole Thorlacius-Ussing
Correct staging of pancreatic cancer is paramount, as treatment is stage specific. However, minimally invasive tools to facilitate staging are lacking. DNA promoter hypermethylation is a hallmark of cancer. The aim of this study is to evaluate promoter hypermethylation in cell-free DNA as a prognostic marker for stage classification of pancreatic adenocarcinoma. Consecutive patients with pancreatic adenocarcinoma were prospectively included. Plasma samples were obtained before diagnostic work-up and treatment...
August 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28851822/protein-kinase-n3-promotes-bone-resorption-by-osteoclasts-in-response-to-wnt5a-ror2-signaling
#11
Shunsuke Uehara, Nobuyuki Udagawa, Hideyuki Mukai, Akihiro Ishihara, Kazuhiro Maeda, Teruhito Yamashita, Kohei Murakami, Michiru Nishita, Takashi Nakamura, Shigeaki Kato, Yasuhiro Minami, Naoyuki Takahashi, Yasuhiro Kobayashi
Cytoskeletal reorganization in osteoclasts to form actin rings is necessary for these cells to attach to bone and resorb bone matrices. We delineated the pathway through which Wnt5a signaling through receptor tyrosine kinase-like orphan receptor 2 (Ror2) promoted the bone-resorbing activity of osteoclasts. Wnt5a binding to Ror2 stimulated Rho, a small GTPase involved in cytoskeletal reorganization. Subsequently, the Rho effector kinase Pkn3 bound to and enhanced the activity of c-Src, a nonreceptor tyrosine kinase that is critical for actin ring formation...
August 29, 2017: Science Signaling
https://www.readbyqxmd.com/read/28846685/myeloid-wnt-ligands-are-required-for-normal-development-of-dermal-lymphatic-vasculature
#12
Ajit Muley, Yoshi Odaka, Ian P Lewkowich, Shruti Vemaraju, Terry P Yamaguchi, Carrie Shawber, Belinda H Dickie, Richard A Lang
Resident tissue myeloid cells play a role in many aspects of physiology including development of the vascular systems. In the blood vasculature, myeloid cells use VEGFC to promote angiogenesis and can use Wnt ligands to control vascular branching and to promote vascular regression. Here we show that myeloid cells also regulate development of the dermal lymphatic vasculature using Wnt ligands. Using myeloid-specific deletion of the WNT transporter Wntless we show that myeloid Wnt ligands are active at two distinct stages of development of the dermal lymphatics...
2017: PloS One
https://www.readbyqxmd.com/read/28833807/the-wnt5a-receptor-ror2-is-a-predictive-cell-surface-marker-of-human-mesenchymal-stem-cells-with-an-enhanced-capacity-for-chondrogenic-differentiation
#13
Sally C Dickinson, Catherine A Sutton, Kyla Brady, Anna Salerno, Theoni Katopodi, Rhys L Williams, Christopher C West, Denis Evseenko, Ling Wu, Suzanna Pang, Roberta Ferro de Godoy, Allen E Goodship, Bruno Péault, Ashley W Blom, Wael Kafienah, Anthony P Hollander
Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However until now their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here we identify ROR2 as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis...
August 20, 2017: Stem Cells
https://www.readbyqxmd.com/read/28810055/impact-of-mir-26b-on-cardiomyocyte-differentiation-in-p19-cells-through-regulating-canonical-non-canonical-wnt-signalling
#14
Duo Wang, Chang Liu, Yumei Wang, Wenjing Wang, Kang Wang, Xiujuan Wu, Zhigang Li, Cuimei Zhao, Li Li, Luying Peng
BACKGROUND AND OBJECTIVES: The control of cardiomyocyte differentiation is tightly linked to microRNAs (miRNAs), which have been emerging as important players in heart development. However, the regulation mechanisms mediated by miRNAs in early heart development remains speculative. Here, we evaluated the impact of miR-26b during the progression of cardiomyocyte differentiation from the P19 cell line. MATERIALS AND METHODS: The overexpression of miR-26b in P19 cells was performed by transduction with lentivirus vector...
August 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28807051/mesenchymal-stromal-cells-ameliorate-oxidative-stress-induced-islet-endothelium-apoptosis-and-functional-impairment-via-wnt4-%C3%AE-catenin-signaling
#15
Lingshu Wang, Li Qing, He Liu, Na Liu, Jingting Qiao, Chen Cui, Tianyi He, Ruxing Zhao, Fuqiang Liu, Fei Yan, Chuan Wang, Kai Liang, Xinghong Guo, Ying H Shen, Xinguo Hou, Li Chen
BACKGROUND: Islet dysfunction and destruction are the common cause for both type 1 and type 2 diabetes mellitus (T2DM). The islets of Langerhans are highly vascularized miniorgans, and preserving the structural integrity and full function of the microvascular endothelium is vital for protecting the islets from the infiltration of immune cells and secondary inflammatory attack. Mesenchymal stromal cell (MSC)-based therapies have been proven to promote angiogenesis of the islets; however, the underlying mechanism for the protective role of MSCs in the islet endothelium is still vague...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28780397/neonatal-exposure-to-a-glyphosate-based-herbicide-alters-uterine-decidualization-in-rats
#16
Paola I Ingaramo, Jorgelina Varayoud, María M Milesi, Marlise Guerrero Schimpf, Ramiro Alarcón, Mónica Muñoz-de-Toro, Enrique H Luque
We investigated whether defective modulation of uterine signaling may cause decidualization failure in rats neonatally exposed to a glyphosate-based herbicide (GBH). Female pups received vehicle or 2mg/kg of GBH from postnatal day (PND) 1 to PND7. On PND8 and PND21, Wnt5a and β-catenin expression was evaluated in uterine samples. On gestational day (GD) 9, Wnt5a, Wnt7a and β-catenin expression and Dkk1 and sFRP4 mRNA were evaluated on implantation sites. On PND8, GBH-exposed rats showed increased Wnt5a and β-catenin expression in luminal epithelium (LE), whereas on PND21, they showed increased Wnt5a and β-catenin expression in subepithelial stroma but decreased β-catenin expression in glandular epithelium...
August 2, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28777797/alteration-of-wnt5a-expression-and-of-the-non-canonical-wnt-pcp-and-wnt-pkc-ca2-pathways-in-human-osteoarthritis-osteoblasts
#17
Xavier Martineau, Élie Abed, Johanne Martel-Pelletier, Jean-Pierre Pelletier, Daniel Lajeunesse
OBJECTIVE: Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts (Ob) is involved in the progression and/or onset of osteoarthritis (OA). Human Ob isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/β-catenin signaling pathway (cWnt), and a reduced mineralization in vitro. In addition to the cWnt pathway, at least two non-canonical signaling pathways, the Wnt/PKC and Wnt/PCP pathway have been described...
2017: PloS One
https://www.readbyqxmd.com/read/28754618/hepatoprotective-effect-of-hesperidin-in-hepatocellular-carcinoma-involvement-of-wnt-signaling-pathways
#18
Randa A Zaghloul, Nehal M Elsherbiny, Hany I Kenawy, Amr El-Karef, Laila A Eissa, Mamdouh M El-Shishtawy
AIMS: Wnt3a and Wnt5a are ligands orchestrating the canonical and non-canonical pathways, respectively, with involvement in hepatocellular carcinoma (HCC). Hesperidin (HP) is a natural product found in citrus fruits and reputed for its antitumor activity. The present study aims to investigate the potential hepatoprotective effect of HP against thioacetamide (TAA)-induced HCC focusing on its potential role on Wnt3a and Wnt5a signaling pathways. MAIN METHODS: Forty rats were equally divided into groups; normal control, HP control (receiving HP, 150mg/kg/day), HCC (receiving TAA, 200mg/kg twice weekly for 14weeks) and HP-HCC (receiving HP and TAA)...
July 25, 2017: Life Sciences
https://www.readbyqxmd.com/read/28748258/ezh2-is-involved-in-silencing-of-wnt5a-during-epithelial-mesenchymal-transition-of-colon-cancer-cell-line
#19
Jianxin Tao, Liping Shi, Longchang Huang, Haoze Shi, Hang Chen, Yixin Wang, Tong Wang
PURPOSE: Transforming growth factor-β (TGF-β) induction of epithelial-mesenchymal transition (EMT) in SW480 was established as a system for studies of colon cancer metastasis. However, the epigenetic mechanisms underlying this process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a highly conserved histone methyltransferase involved in epigenetic regulations. Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which catalyzes methylation of lysine 27 of histone H3 (H3K27)...
July 26, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28736081/frizzled-7-mediates-tgf-%C3%AE-induced-pulmonary-fibrosis-by-transmitting-non-canonical-wnt-signaling
#20
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
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