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Wnt/b-catenin signal

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https://www.readbyqxmd.com/read/29684621/setd7-and-its-contribution-to-boron-induced-bone-regeneration-in-b-mbg-scaffolds
#1
Chengcheng Yin, Xiaoshi Jia, Richard J Miron, Qiaoyun Long, Hudi Xu, Yan Wei, Min Wu, Yufeng Zhang, Zubing Li
Boron (B), a trace element found in the human body, plays an important role for health of bone by promoting the proliferation and differentiation of osteoblasts. Our research group previously fabricated B-mesoporous bioactive glass (MBG) scaffolds, which successfully promoted osteogenic differentiation of osteoblasts when compared to pure MBG scaffolds without boron. However, the mechanisms of the positive effect of B-MBG scaffolds on osteogenesis remains unknown. Therefore, we performed in-vivo experiments in an OVX rat models with pure MBG scaffolds and compared them to B-MBG scaffold...
April 20, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29668981/wnts-role-in-bovine-folliculogenesis-and-estrogen-production
#2
B I Gomez, B H Aloqaily, C A Gifford, D M Hallford, J A Hernandez Gifford
Appreciation of mechanisms that affect steroidogenesis is critical to identifying compromising signals that may decrease reproductive efficiency. Follicle maturation and steroidogenesis requires coordinated actions from the pituitary gonadotropins, and local ovarian signaling molecules. Beta-catenin (CTNNB1), the lynchpin molecule of canonical wingless-type mouse mammary tumor virus integration site (WNT) signaling is required for maximal gonadotropin stimulation of steroid production from granulosa (GC) and luteal cells...
April 13, 2018: Journal of Animal Science
https://www.readbyqxmd.com/read/29666061/deptor-is-a-novel-target-of-wnt-%C3%AE-catenin-c-myc-and-contributes-to-colorectal-cancer-cell-growth
#3
Qingding Wang, Yuning Zhou, Piotr Rychahou, Jennifer W Harris, Yekaterina Y Zaytseva, Jinpeng Liu, Chi Wang, Heidi L Weiss, Chunming Liu, Eun Y Lee, B Mark Evers
Activation of the Wnt/β-catenin signaling pathway drives colorectal cancer (CRC) growth by deregulating expression of downstream target genes including the c-Myc proto-oncogene. The critical targets that mediate the functions of oncogenic c-Myc in CRC have yet to be fully elucidated. Previously, we showed that activation of PI3K/Akt/mTOR contributes to CRC growth and metastasis. Here we show that Deptor, a suppressor of mTOR, is a direct target of Wnt/β-catenin/c-Myc signaling in CRC cells. Inhibition of Wnt/β-catenin or knockdown of c-Myc decreased, while activation of Wnt/β-catenin or overexpression of c-Myc increased, the expression of Deptor...
April 17, 2018: Cancer Research
https://www.readbyqxmd.com/read/29662489/immunological-approaches-towards-cancer-and-inflammation-a-cross-talk
#4
REVIEW
Xinglong Qu, Ying Tang, Shucheng Hua
The inflammation is the protective response of the body against various harmful stimuli; however, the aberrant and inappropriate activation tends to become harmful. The acute inflammatory response tends to resolved once the offending agent is subside but this acute response becomes chronic in nature when the body is unable to successfully neutralized the noxious stimuli. This chronic inflammatory microenvironment is associated with the release of various pro-inflammatory and oncogenic mediators such as nitric oxide (NO), cytokines [IL-1β, IL-2, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)], growth factor, and chemokines...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29642538/ddx5-rna-helicases-emerging-roles-in-viral-infection
#5
REVIEW
Wenyu Cheng, Guohua Chen, Huaijie Jia, Xiaobing He, Zhizhong Jing
Asp-Glu-Ala-Asp (DEAD)-box polypeptide 5 (DDX5), also called p68, is a prototypical member of the large ATP-dependent RNA helicases family and is known to participate in all aspects of RNA metabolism ranging from transcription to translation, RNA decay, and miRNA processing. The roles of DDX5 in cell cycle regulation, tumorigenesis, apoptosis, cancer development, adipogenesis, Wnt-β-catenin signaling, and viral infection have been established. Several RNA viruses have been reported to hijack DDX5 to facilitate various steps of their replication cycles...
April 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29642462/new-challenges-in-targeting-signaling-pathways-in-acute-lymphoblastic-leukemia-by-ngs-approaches-an-update
#6
REVIEW
Adrián Montaño, Maribel Forero-Castro, Darnel Marchena-Mendoza, Rocío Benito, Jesús María Hernández-Rivas
The identification and study of genetic alterations involved in various signaling pathways associated with the pathogenesis of acute lymphoblastic leukemia (ALL) and the application of recent next-generation sequencing (NGS) in the identification of these lesions not only broaden our understanding of the involvement of various genetic alterations in the pathogenesis of the disease but also identify new therapeutic targets for future clinical trials. The present review describes the main deletions, amplifications, sequence mutations, epigenetic lesions, and new structural DNA rearrangements detected by NGS in B-ALL and T-ALL and their clinical importance for therapeutic procedures...
April 7, 2018: Cancers
https://www.readbyqxmd.com/read/29620204/tenascin%C3%A2-c-promotes-the-migration-of-bone-marrow-stem-cells-via-toll%C3%A2-like-receptor-4%C3%A2-mediated-signaling-pathways-mapk-akt-and-wnt
#7
Huaiyu Ding, Mingyu Jin, Dai Liu, Shujing Wang, Jianing Zhang, Xiantao Song, Rongchong Huang
There are currently limitations in stem cell therapy due to the low rate of homing and proliferation of cells following transplantation. The present study was designed to investigate the effects of Tenascin‑C (TN‑C) on bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. BMSCs were obtained from C57BL/6 mice. The survival and proliferation of BMSCs was analyzed by Cell Counting Kit‑8 assay, migration was evaluated using the Transwell method, and differentiation was assessed by immunocytochemistry and immunofluorescence...
April 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29617376/brain-tumor-promotes-axon-growth-across-the-midline-through-interactions-with-the-microtubule-stabilizing-protein-apc2
#8
Elise Arbeille, Greg J Bashaw
Commissural axons must cross the midline to establish reciprocal connections between the two sides of the body. This process is highly conserved between invertebrates and vertebrates and depends on guidance cues and their receptors to instruct axon trajectories. The DCC family receptor Frazzled (Fra) signals chemoattraction and promotes midline crossing in response to its ligand Netrin. However, in Netrin or fra mutants, the loss of crossing is incomplete, suggesting the existence of additional pathways. Here, we identify Brain Tumor (Brat), a tripartite motif protein, as a new regulator of midline crossing in the Drosophila CNS...
April 4, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29601474/lgr5-and-bmi1-increase-pig-intestinal-epithelial-cell-proliferation-by-stimulating-wnt-%C3%AE-catenin-signaling
#9
Xiang-Guang Li, Zhe Wang, Rong-Qiang Chen, Hou-Long Fu, Chun-Qi Gao, Hui-Chao Yan, Guang-Xu Xing, Xiu-Qi Wang
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) are markers of fast-cycling and quiescent intestinal stem cells, respectively. To determine the functions of these proteins in large animals, we investigated their effects on the proliferation of intestinal epithelial cells from pigs. Our results indicated that LGR5 and BMI1 are highly conserved proteins and that the pig proteins have greater homology with the human proteins than do mouse proteins...
March 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29566337/structure-based-optimization-of-small-molecule-inhibitors-for-the-%C3%AE-catenin-b-cell-lymphoma-9-protein-protein-interaction
#10
Min Zhang, Zhen Wang, Yongqiang Zhang, Wenxing Guo, Haitao Ji
Structure-based optimization was conducted to improve the potency, selectivity, and cell-based activities of β-catenin/B-cell lymphoma 9 (BCL9) inhibitors based on the 4'-fluoro-N-phenyl-[1,1'-biphenyl]-3-carboxamide scaffold, which was designed to mimic the side chains of the hydrophobic α-helical hot spots at positions i, i + 3, and i + 7. Compound 29 was found to disrupt the β-catenin/BCL9 protein-protein interaction (PPI) with a Ki of 0.47 μM and >1900-fold selectivity for β-catenin/BCL9 over β-catenin/E-cadherin PPIs...
March 22, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29565486/microrna-338-inhibits-proliferation-migration-and-invasion-of-gastric-cancer-cells-by-the-wnt-%C3%AE-catenin-signaling-pathway
#11
B Song, H-X Lin, L-L Dong, J-J Ma, Z-G Jiang
OBJECTIVE: Emerging evidence suggests aberrant microRNAs (miRNAs) expression is involved in cancer development through multiple. Although miR338 has shown to have tumor suppression ability and anti-migration effects in some cancers, its regulatory role and molecular mechanism in the development of gastric cancer cells yet remains little known. This work aims to investigate miR-338 in regulating Wnt/β-catenin pathway in epithelial-mesenchymal transition (EMT) in gastric cancers. MATERIALS AND METHODS: Human gastric cancer cells were transfected with either miR-338 mimic or erythropoietin-producing hepatocellular (Eph)A2-targeting siRNA...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29549490/androgen-modulation-of-wnt-%C3%AE-catenin-signaling-in-androgenetic-alopecia
#12
REVIEW
A Premanand, B Reena Rajkumari
Androgenetic alopecia (AGA) is a dermatological disorder of scalp hair loss characterized by a progressive miniaturization of hair follicles with shortened anagen phase leading to a decreased number of hairs on the scalp. It is a complex polygenic trait prevailing around two-thirds of the male population. Elevated expressions of 5α-dihydrotestosterone and androgen receptor are the causal factors for AGA. This review describes recent studies on the role of androgens and androgen receptor (AR) transactivation activity in modulating the Wnt/β-catenin signaling in the dermal papilla cells of the balding scalp in androgenetic alopecia...
March 16, 2018: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29524295/mical1-facilitates-breast-cancer-cell-proliferation-via-ros-sensitive-erk-cyclin-d-pathway
#13
Wenjie Deng, Yueyuan Wang, Shuo Zhao, Yujie Zhang, Yan Chen, Xuyang Zhao, Lei Liu, Shixiu Sun, Lin Zhang, Bixing Ye, Jun Du
Molecule interacting with CasL 1 (MICAL1) is a multidomain flavoprotein mono-oxygenase that strongly involves in cytoskeleton dynamics and cell oxidoreduction metabolism. Recently, results from our laboratory have shown that MICAL1 modulates reactive oxygen species (ROS) production, and the latter then activates phosphatidyl inositol 3-kinase (PI3K)/protein kinase B (Akt) signalling pathway which regulates breast cancer cell invasion. Herein, we performed this study to assess the involvement of MICAL1 in breast cancer cell proliferation and to explore the potential molecular mechanism...
March 10, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29510987/genetic-mechanisms-of-immune-evasion-in-colorectal-cancer
#14
Catherine S Grasso, Marios Giannakis, Daniel K Wells, Tsuyoshi Hamada, Xinmeng Jasmine Mu, Michael Quist, Jonathan A Nowak, Reiko Nishihara, Zhi Rong Qian, Kentaro Inamura, Teppei Morikawa, Katsuhiko Nosho, Gabriel Abril-Rodriguez, Charles Connolly, Helena Escuin-Ordinas, Milan S Geybels, William M Grady, Li Hsu, Siwen Hu-Lieskovan, Jeroen R Huyghe, Yeon Joo Kim, Paige E Krystofinski, Mark Dm Leiserson, Dennis J Montoya, Brian B Nadel, Matteo Pellegrini, Colin C Pritchard, Cristina Puig-Saus, Elleanor H Quist, Benjamin J Raphael, Stephen J Salipante, Daniel Sanghoon Shin, Eve Shinbrot, Brian Shirts, Sachet Shukla, Janet L Stanford, Wei Sun, Jennifer Tsoi, Alexander Upfill-Brown, David A Wheeler, Catherine J Wu, Ming Yu, Syed H Zaidi, Jesse M Zaretsky, Stacey B Gabriel, Eric S Lander, Levi A Garraway, Thomas J Hudson, Charles S Fuchs, Antoni Ribas, Shuji Ogino, Ulrike Peters
To understand the genetic drivers of immune recognition and evasion in colorectal cancer (CRC), we analyzed 1,211 CRC primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas CRC cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of CRC, had a high rate of significantly mutated genes in important immune modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy number alterations and copy-neutral loss of heterozygosity (CN-LOH)...
March 6, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29510447/proteomic-analysis-reveals-a-strong-association-of-%C3%AE-catenin-with-cadherin-adherens-junctions-in-resting-human-platelets
#15
Patricia B Maguire, Tim Donlon, Martin Parsons, Kieran Wynne, Eugene Dillon, Fionnuala Ní Áinle, Paulina B Szklanna
We previously demonstrated that the WNT/β-catenin pathway is present and active in platelets and established that the canonical WNT ligand, WNT-3a, suppresses platelet adhesion and activation. In nucleated cells, β-catenin, the key downstream effector of this pathway, is a dual function protein, regulating the coordination of gene transcription and cell-cell adhesion. The specific role of β-catenin in the anucleate platelet however remains elusive. Here, we performed a label-free quantitative proteomic analysis of β-catenin immunoprecipitates from human platelets and identified 9 co-immunoprecipitating proteins...
March 6, 2018: Proteomics
https://www.readbyqxmd.com/read/29483204/mir-103-107-promote-er-stress-mediated-apoptosis-via-targeting-the-wnt3a-%C3%AE-catenin-atf6-pathway-in-preadipocytes
#16
Zhenzhen Zhang, Song Wu, Saeed Muhammad, Qian Ren, Chao Sun
Both miR-103 and 107 have been demonstrated to restrain cell proliferation, regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocytes apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocytes apoptosis. We found that miR-103/107 aggravated Endoplasmic Reticulum (ER) stress mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted Wnt3a (WNT family member 3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes...
February 26, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29463558/disruption-of-wnt-%C3%AE-catenin-exerts-antileukemia-activity-and-synergizes-with-flt3-inhibition-in-flt3-mutant-acute-myeloid-leukemia
#17
Xuejie Jiang, Po Yee Mak, Hong Mu, Wenjing Tao, Duncan H Mak, Steven Kornblau, Qi Zhang, Peter Ruvolo, Jared K Burks, Weiguo Zhang, Teresa McQueen, Rongqing Pan, Hongsheng Zhou, Marina Konopleva, Jorge Cortes, Qifa Liu, Michael Andreeff, Bing Z Carter
Purpose: Wnt/β-catenin signaling is required for leukemic stem cell function. FLT3 mutations are frequently observed in acute myeloid leukemia (AML). Anomalous FLT3 signaling increases β-catenin nuclear localization and transcriptional activity. FLT3 tyrosine kinase inhibitors (TKI) are used clinically to treat FLT3 -mutated AML patients, but with limited efficacy. We investigated the antileukemia activity of combined Wnt/β-catenin and FLT3 inhibition in FLT3 -mutant AML. Experimental Design: Wnt/β-catenin signaling was inhibited by the β-catenin/CBP antagonist C-82/PRI-724 or siRNAs, and FLT3 signaling by sorafenib or quizartinib...
February 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29454609/deubiquitinase-inhibitor-b-ap15-activates-endoplasmic-reticulum-er-stress-and-inhibits-wnt-notch1-signaling-pathway-leading-to-the-reduction-of-cell-survival-in-hepatocellular-carcinoma-cells
#18
Youming Ding, Xiaoyan Chen, Bin Wang, Bin Yu, Jianhui Ge
b-AP15, a potent and selective inhibitor of the ubiquitin-specific peptidase 14 (USP14), displays in vitro and in vivo antitumor abilities on some types of cancer cells. However, the mechanism underlying its action is not well elucidated. The purposes of the present study are to observe the potential impacts of b-AP15 on cell survival of hepatocellular carcinoma cells and to investigate whether and how this compound inhibits some survival-promoting signaling pathways. We found that b-AP15 significantly decreased cell viability and increased cell apoptosis in a dose-dependent manner in hepatocellular carcinoma cells, along with the perturbation of cell cycle and the decreased expressions of cell cycle-related proteins...
February 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29453334/%C3%AE-catenin-independent-regulation-of-wnt-target-genes-by-ror2-and-atf2-atf4-in-colon-cancer-cells
#19
Oksana Voloshanenko, Uwe Schwartz, Dominique Kranz, Benedikt Rauscher, Michael Linnebacher, Iris Augustin, Michael Boutros
Wnt signaling is an evolutionarily conserved signaling route required for development and homeostasis. While canonical, β-catenin-dependent Wnt signaling is well studied and has been linked to many forms of cancer, much less is known about the role of non-canonical, β-catenin-independent Wnt signaling. Here, we aimed at identifying a β-catenin-independent Wnt target gene signature in order to understand the functional significance of non-canonical signaling in colon cancer cells. Gene expression profiling was performed after silencing of key components of Wnt signaling pathway and an iterative signature algorithm was applied to predict pathway-dependent gene signatures...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29438981/pgam5-released-from-damaged-mitochondria-induces-mitochondrial-biogenesis-via-wnt-signaling
#20
Dominic B Bernkopf, Kowcee Jalal, Martina Brückner, Karl X Knaup, Marc Gentzel, Alexandra Schambony, Jürgen Behrens
Mitochondrial abundance is dynamically regulated and was previously shown to be increased by Wnt/β-catenin signaling. Pgam5 is a mitochondrial phosphatase which is cleaved by the rhomboid protease presenilin-associated rhomboid-like protein (PARL) and released from membranes after mitochondrial stress. In this study, we show that Pgam5 interacts with the Wnt pathway component axin in the cytosol, blocks axin-mediated β-catenin degradation, and increases β-catenin levels and β-catenin-dependent transcription...
February 8, 2018: Journal of Cell Biology
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