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Wnt activators

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https://www.readbyqxmd.com/read/29150975/downregulation-of-dusp4-enhances-cell-proliferation-and-invasiveness-in-colorectal-carcinomas
#1
Michihiro Ichimanda, Naoki Hijiya, Yoshiyuki Tsukamoto, Tomohisa Uchida, Chisato Nakada, Tomonori Akagi, Tsuyoshi Etoh, Hidekatsu Iha, Masafumi Inomata, Mutsuhiro Takekawa, Masatsugu Moriyama
It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas...
November 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/29149835/forkhead-transcription-factors-formulating-a-foxo-target-for-cognitive-loss
#2
Kenneth Maiese
BACKGROUND: With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. METHODS: Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29148535/the-role-of-apc-in-wnt-pathway-activation-in-serrated-neoplasia
#3
Jennifer Borowsky, Troy Dumenil, Mark Bettington, Sally-Ann Pearson, Catherine Bond, Lochlan Fennell, Cheng Liu, Diane McKeone, Christophe Rosty, Ian Brown, Neal Walker, Barbara Leggett, Vicki Whitehall
Conventional adenomas are initiated by APC gene mutation that activates the WNT signal. Serrated neoplasia is commonly initiated by BRAF or KRAS mutation. WNT pathway activation may also occur, however, to what extent this is owing to APC mutation is unknown. We examined aberrant nuclear β-catenin immunolocalization as a surrogate for WNT pathway activation and analyzed the entire APC gene coding sequence in serrated and conventional pathway polyps and cancers. WNT pathway activation was a common event in conventional pathway lesions with aberrant nuclear immunolocalization of β-catenin and truncating APC mutations in 90% and 89% of conventional adenomas and 82% and 70% of BRAF wild-type cancers, respectively...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29147753/defective-wnt-signaling-associates-with-bone-marrow-fibrosis-a-cross-sectional-cohort-study-in-a-family-with-wnt1-osteoporosis
#4
R E Mäkitie, R Niinimäki, S Kakko, T Honkanen, P E Kovanen, O Mäkitie
This study explores bone marrow function in patients with defective WNT1 signaling. Bone marrow samples showed increased reticulin and altered granulopoiesis while overall hematopoiesis was normal. Findings did not associate with severity of osteoporosis. These observations provide new insight into the role of WNT signaling in bone marrow homeostasis. INTRODUCTION: WNT signaling regulates bone homeostasis and survival and self-renewal of hematopoietic stem cells. Aberrant activation may lead to osteoporosis and bone marrow pathology...
November 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/29146058/methylation-associated-silencing-of-sfrp1-gene-in-high-grade-serous-ovarian-carcinomas
#5
Vedran Kardum, Valentina Karin, Mislav Glibo, Anita Skrtic, Tamara Nikuseva Martic, Nermina Ibisevic, Faruk Skenderi, Semir Vranic, Ljiljana Serman
Wnt is a highly conserved signaling pathway responsible for tissue regeneration, maintenance and differentiation of stem cells in adults. Its aberrant activation through reduced expression of Wnt signaling pathway inhibitors, such as proteins from the SFRP family, is commonly seen in many tumors. In the present study we explored SFRP1 protein expression using immunohistochemistry in 11 low-grade serous ovarian carcinomas (LGSC), 42 high-grade serous ovarian carcinomas (HGSC), and 5 normal ovarian tissues (controls)...
December 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29145973/tak-ing-aim-at-chemoresistance-the-emerging-role-of-map3k7-as-a-target-for-cancer-therapy
#6
Raffaela Santoro, Carmine Carbone, Geny Piro, Paul J Chiao, Davide Melisi
Cellular drug resistance remains the main obstacle to the clinical efficacy of cancer chemotherapy. Alterations in key pathways regulating cell cycle checkpoints, apoptosis and Epithelial to Mesenchymal Transition (EMT), such as the Mitogen-activated protein kinase (MAPK) pathway, appear to be closely associated to cancer chemoresistance. Transforming growth factor-β (TGF-β)- activated kinase 1 (TAK1, also known as MAP3K7) is a serine/threonine kinase in the mitogen-activated protein kinase (MAP3K) family...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145436/scrambled-eggs-proteomic-portraits-and-novel-biomarkers-of-egg-quality-in-zebrafish-danio-rerio
#7
Ozlem Yilmaz, Amélie Patinote, Thao Vi Nguyen, Emmanuelle Com, Regis Lavigne, Charles Pineau, Craig V Sullivan, Julien Bobe
Egg quality is a complex biological trait and a major determinant of reproductive fitness in all animals. This study delivered the first proteomic portraits of egg quality in zebrafish, a leading biomedical model for early development. Egg batches of good and poor quality, evidenced by embryo survival for 24 h, were sampled immediately after spawning and used to create pooled or replicated sample sets whose protein extracts were subjected to different levels of fractionation before liquid chromatography and tandem mass spectrometry...
2017: PloS One
https://www.readbyqxmd.com/read/29145164/long-noncoding-rna-hnf1a-as1-indicates-a-poor-prognosis-of-colorectal-cancer-and-promotes-carcinogenesis-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#8
Xin Zhang, Yumin Xiong, Fengying Tang, Ying Bian, Yanhui Chen, Fengli Zhang
Long non-coding RNAs (lncRNAs) have been identified to play critical roles in tumorigenesis. LncRNA HNF1A-AS1 has been suggested to act as an oncogene and serves as a novel prognostic biomarker for various cancer. However, the biological role and clinical significance of lncRNA HNF1A-AS1 in colorectal cancer (CRC) have yet to be fully elusive. Therefore, the present study was designed to determine the expression of lncRNA HNF1A-AS1 in patients with CRC, the role of lncRNA HNF1A-AS1 in CRC cells, as well as the underlying regulatory mechanisms...
October 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29144570/lncapc-drives-wnt-%C3%AE-catenin-activation-and-liver-tic-self-renewal-through-ezh2-mediated-apc-transcriptional-inhibition
#9
Xiaomin Fu, Jizhen Lin, Fujun Qin, Zihe Yang, Yuechao Ding, Yong Zhang, Lu Han, Xiaoyan Zhu, Qinxian Zhang
Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling...
November 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29143994/intermittent-compressive-force-induces-human-mandibular-derived-osteoblast-differentiation-via-wnt-%C3%AE-catenin-signaling
#10
Pimrumpai Rochanakit Sindhavajiva, Panunn Sastravaha, Mansuang Arksornnukit, Prasit Pavasant
Mechanical force induces an efflux of ATP that regulates osteoblast differentiation. However, the effect of mechanical force-induced ATP efflux on WNT/β-catenin signaling remains unclarified. The aim of this study was to investigate the effect of intermittent compressive force (ICF) and ICF-induced extracellular ATP on osteoblast differentiation via WNT/β-catenin signaling in human mandibular-derived osteoblast precursors (hMOBPs). The hMOBPs were subjected to ICF (1.5 g/cm(2) , 0.3 Hz) for 20 h. To investigate the role of ATP, Apyrase (0...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143549/negative-impact-of-hyperglycaemia-on-mouse-alveolar-development
#11
Mei-Yao He, Guang Wang, Sha-Sha Han, Ke Li, Ya Jin, Meng Liu, Zhen-Peng Si, Ju Wang, Guo-Sheng Liu, Xuesong Yang
Diabetes mellitus in pregnancy has been known to affect the embryonic development of various systems, including cardiovascular and nervous systems. However, whether this disease could have a negative impact on embryonic respiratory system remains controversial. In this study, we demonstrated that pregestational diabetes mellitus (PGDM)-induced defects in lung development in mice are mainly characterized by the changes in the morphological structure of the lung. Immunostaining and Western blotting showed that proliferation increased and apoptosis decreased in PGDM...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29142600/co-activation-of-hedgehog-and-wnt-signaling-pathways-is-associated-with-poor-outcomes-in-triple-negative-breast-cancer
#12
Kimberly M Arnold, Ryan T Pohlig, Jennifer Sims-Mourtada
Hedgehog (HH) and Wnt pathway activation have been implicated in poor prognosis of breast cancer. Crosstalk between these two pathways has been demonstrated to be important in breast cancer progression, however the association between these two pathways and breast cancer survival rate is unknown. The present study comprised a cohort of 36 patients with triple negative breast cancer (TNBC) to investigate co-activation of HH and canonical Wnt pathway in association to patient outcome. All patients had varying degrees of cytoplasmic sonic HH and glioma-associated oncogene homolog (Gli)-1 staining, which positively correlated with tumor stage...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142233/crystal-structure-of-the-n-terminal-domain-of-human-cdc73-and-its-implications-for-the-hyperparathyroidism-jaw-tumor-hpt-jt-syndrome
#13
Wei Sun, Xiao-Lin Kuang, Yan-Ping Liu, Li-Fei Tian, Xiao-Xue Yan, Wenqing Xu
CDC73/Parafibromin is a critical component of the Paf1 complex (PAF1C), which is involved in transcriptional elongation and histone modifications. Mutations of the human CDC73/HRPT2 gene are associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disorder. CDC73/parafibromin was initially recognized as a tumor suppressor by inhibiting cell proliferation via repression of cyclin D1 and c-myc genes. In recent years, it has also shown oncogenic features by activating the canonical Wnt/β-catenin signal pathway...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141533/targeting-cancer-stem-cells-and-non-stem-cancer-cells-the-potential-of-lipid-based-nanoparticles
#14
Ana Filipa Cruz, Nuno Andre Fonseca, Vera Moura, Sergio Simoes, Joao Nuno Moreira
Background Cancer stem cells (CSCs) have been described as a relevant contributor to tumorigenicity, metastasis, tumor recurrence and drug resistance, making this cell population a relevant target in solid tumors. METHODS: This has stimulated the development of different therapeutic strategies often targeting surface markers (CD44, epithelial cell adhesion molecule (EpCAM), aldehyde dehydrogenase (ALDH) and nucleolin) and/or signaling pathways that are aberrantly activated and contribute to CSCs proliferation and survival...
November 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29141367/-differentiation-of-induced-pluripotent-stem-cells-into-neural-stem-cells-induced-by-brain-derived-neurotrophic-factor-via-wnt-%C3%AE-catenin-and-extracellular-signal-regulated-kinase-mitogen-activated-protein-kinases-signal-pathway
#15
S Q Chen, M Huang, C L Liu, Y Y Shen, Q Cai, P J Wang
Objective: To investigate the mechanism of brain-derived neurotrophic factor (BDNF) promoting induced pluripotent stem cells (iPSCs) to differentiate into neural stem cells (NSCs) via Wnt/β-catenin and extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK) signal pathways. Methods: iPSCs were cultured and identified. The iPSCs were induced to differentiate into NSCs by BDNF and retinoic acid (RA). Nestin was detected by immunofluorescence and flow cytometry after iPSCs differentiated...
November 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29141249/%C3%AE-catenin-cooperates-with-creb-binding-protein-to-promote-the-growth-of-tumor-cells
#16
Wendan Yu, Liren Li, Fufu Zheng, Wenjing Yang, Shilei Zhao, Chunfang Tian, Wenwen Yin, Yiming Chen, Wei Guo, Lijuan Zou, Wuguo Deng
BACKGROUND/AIMS: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29139535/contribution-of-cranial-neural-crest-cells-to-mouse-skull-development
#17
Taofen Wu, Guiqian Chen, Fei Tian, Hong-Xiang Liu
The mammalian skull vault is a highly regulated structure that evolutionally protects brain growth during vertebrate development. It consists of several membrane bones with different tissue origins (e.g. neural crest-derived frontal bone and mesoderm-derived parietal bone). Although membrane bones are formed through intramembranous ossification, the neural crest-derived frontal bone has superior capabilities for osteoblast activities and bone regeneration via TGF, BMP, Wnt, and FGF signaling pathways. Neural crest (NC) cells are multipotent, and once induced, will follow specific paths to migrate to different locations of the body where they give rise to a diverse array of cell types and tissues...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29138567/resveratrol-ameliorates-chronic-unpredictable-mild-stress-induced-depression-like-behavior-involvement-of-the-hpa-axis-inflammatory-markers-bdnf-and-wnt-%C3%AE-catenin-pathway-in-rats
#18
Xin-Hua Yang, Su-Qi Song, Yun Xu
Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29138341/long-non-coding-rna-neat1-regulated-by-the-egfr-pathway-contributes-to-glioblastoma-progression-through-the-wnt-%C3%AE-catenin-pathway-by-scaffolding-ezh2
#19
Qun Chen, Jinquan Cai, Qixue Wang, Yunfei Wang, Mingyang Liu, Jingxuan Yang, Junhu Zhou, Chun-Sheng Kang, Min Li, Chuanlu Jiang
PURPOSE: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression datasets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. EXPERIMENTAL DESIGN: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-Catenin pathway and its target binding gene...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137395/lithium-chloride-inhibits-titanium-particle-induced-osteoclastogenesis-by-inhibiting-the-nf-%C3%AE%C2%BAb-pathway
#20
Xuanyang Hu, Zhirong Wang, Jiawei Shi, Xiaobin Guo, Liangliang Wang, Zichuan Ping, Yunxia Tao, Huilin Yang, Jun Zhou, Yaozeng Xu, Dechun Geng
Osteoclast over-activation and inflammation responses promote peri-implant osteolysis (PIO), which is the leading cause of aseptic artificial joint loosening. We examined the effect of lithium chloride (LiCl) on wear debris-induced osteoclastogenesis and inflammation. Fifty-Six C57BL/6J male mice were randomly distributed into four groups: sham control (sham, treated with phosphate buffered saline [PBS]), vehicle (treated with titanium/PBS), low-LiCl (L-LiCl, titanium: 50 mg/kg LiCl) and high-LiCl (H-LiCl, titanium: 200 mg/kg LiCl)...
October 13, 2017: Oncotarget
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