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Wnt activators

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https://www.readbyqxmd.com/read/28545029/tusc3-induces-autophagy-in-human-non-small-cell-lung-cancer-cells-through-wnt-%C3%AE-catenin-signaling
#1
Yun Peng, Jun Cao, Xiao-Yi Yao, Jian-Xin Wang, Mei-Zuo Zhong, Ping-Ping Gan, Jian-Huang Li
We investigated the effects of tumor suppressor candidate 3 (TUSC3) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28543390/the-effect-of-ebv-on-wif1-nlk-and-apc-gene-methylation-and-expression-in-gastric-carcinoma-and-nasopharyngeal-cancer
#2
Zhenzhen Zhao, Wen Liu, Jincheng Liu, Jiayi Wang, Bing Luo
Epstein-Barr virus (EBV) is an important DNA tumor virus that is associated with approximately 10% of gastric carcinomas and 99% of nasopharyngeal cancers. DNA methylation and microRNAs (miRNAs) are the most studied epigenetic mechanisms that can prompt disease susceptibility. This study aimed to detect the effect of EBV on Wnt inhibitory factor 1 (WIF1), Nemo-like kinase (NLK), and adenomatous polyposis coli (APC) gene methylation and expression in gastric carcinoma and nasopharyngeal cancer. METHODS: The WIF1, NLK, and APC gene mRNA expression levels were measured by real-time quantitative RT-PCR in four EBV-positive cell lines and four EBV-negative cell lines...
May 23, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28541575/xenobiotic-car-activators-induce-dlk1-dio3-locus-non-coding-rna-expression-in-mouse-liver
#3
Lucie Pouché, Antonio Vitobello, Michael Römer, Milica Glogovac, A Kenneth MacLeod, Heidrun Ellinger-Ziegelbauer, Magdalena Westphal, Valérie Dubost, Daniel Philipp Stiehl, Bérengère Dumotier, Alexander Fekete, Pierre Moulin, Andreas Zell, Michael Schwarz, Rita Moreno, Jeffrey T J Huang, Cliff R Elcombe, Colin J Henderson, C Roland Wolf, Jonathan G Moggs, Rémi Terranova
Derisking xenobiotic-induced non-genotoxic carcinogenesis (NGC) represents a significant challenge during the safety assessment of chemicals and therapeutic drugs. The identification of robust mechanism-based NGC biomarkers has the potential to enhance cancer hazard identification. We previously demonstrated Constitutive Androstane Receptor (CAR) and WNT signaling-dependent up-regulation of the pluripotency associated Dlk1-Dio3 imprinted gene cluster non-coding RNAs (ncRNAs) in the liver of mice treated with tumor-promoting doses of phenobarbital (PB)...
May 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28540808/exposure-to-febrile-range-hyperthermia-potentiates-wnt-signalling-and-epithelial-mesenchymal-transition-gene-expression-in-lung-epithelium
#4
Ratnakar Potla, Mohan E Tulapurkar, Irina G Luzina, Sergei P Atamas, Ishwar S Singh, Jeffrey D Hasday
BACKGROUND: As environmental and body temperatures vary, lung epithelial cells experience temperatures significantly different from normal core temperature. Our previous studies in human lung epithelium showed that: (i) heat shock accelerates wound healing and activates profibrotic gene expression through heat shock factor-1 (HSF1); (ii) HSF1 is activated at febrile temperatures (38-41 °C) and (iii) hypothermia (32 °C) activates and hyperthermia (39.5 °C) reduces expression of a subset of miRNAs that target protein kinase-Cα (PKCα) and enhance proliferation...
April 26, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28540322/targeting-wnt-%C3%AE-catenin-activated-cells-with-dominant-negative-n-cadherin-to-reduce-neointima-formation
#5
Sarah Hulin-Curtis, Helen Williams, Kerry S Wadey, Graciela B Sala-Newby, Sarah J George
Approximately 50% of coronary artery bypass grafts using the autologous saphenous vein fail within 10 years due to intimal thickening. This study examined whether a gene therapy approach that selectively kills Wnt/β-catenin/T cell factor (TCF) activated vascular smooth muscle cells (VSMCs) using dominant-negative N-cadherin (dn-N-cadherin) reduced intimal thickening. Cultured human VSMCs infected with an adenovirus (Ad) encoding dn-N-cadherin via the TCF promoter (Ad-TOP-dn-N-cadherin) specifically expressed dn-N-cadherin in response to activation of the Wnt/β-catenin/TCF pathway...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28539830/dna-methylation-mediated-down-regulation-of-mir-370-regulates-cell-growth-through-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway-in-human-osteosarcoma-cells
#6
Wentao Zhang, Ning Duan, Qian Zhang, Tao Song, Zhong Li, Caiguo Zhang, Xun Chen, Kunzheng Wang
MicroRNA-370 (miR-370) has been observed to act as a tumor suppressor through the targeting of different proteins in a variety of tumors. Our previous study indicated that miR-370 was able to target forkhead box protein M1 (FOXM1) to inhibit cell growth and metastasis in human osteosarcoma cells. In this study, we reported that FOXM1 interacted with β-catenin in vitro and in vivo. Similar to FOXM1, critical components of the Wnt signaling pathway, including β-catenin, c-Myc, and Cyclin D1, were also highly expressed in different human osteosarcoma cells lines...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28539263/nutrients-neurogenesis-and-brain-ageing-from-disease-mechanisms-to-therapeutic-opportunities
#7
REVIEW
Marco Fidaleo, Virve Cavallucci, Giovambattista Pani
Appreciation of the physiological relevance of mammalian adult neurogenesis has in recent years rapidly expanded from a phenomenon of homeostatic cell replacement and brain repair to the current view of a complex process involved in high order cognitive functions. In parallel, an array of endogenous or exogenous triggers of neurogenesis have also been identified, among which metabolic and nutritional cues have drawn significant attention. Converging evidence from animal and in vitro studies point to nutrient sensing and energy metabolism as major physiological determinants of neural stem cell fate, and modulators of the whole neurogenic process...
May 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28536466/fipronil-induced-enantioselective-developmental-toxicity-to-zebrafish-embryo-larvae-involves-changes-in-dna-methylation
#8
Yi Qian, Cui Wang, Jinghua Wang, Xiaofeng Zhang, Zhiqiang Zhou, Meirong Zhao, Chensheng Lu
Enantioselectivity in the aquatic toxicity of chiral pesticides has been widely investigated, while the molecular mechanisms remain unclear. Thus far, few studies has focused on genomic expression related to selective toxicity in chiral pesticide, nor on epigenetic changes, such as DNA methylation. Here, we used fipronil, a broad-spectrum insecticide, as a model chemical to probe its enantioselective toxicity in embryo development. Our results showed that S-(+)-fipronil caused severer developmental toxicity in embryos...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536422/secreted-frizzled-related-protein-4-sfrp4-chemo-sensitizes-cancer-stem-cells-derived-from-human-breast-prostate-and-ovary-tumor-cell-lines
#9
A Deshmukh, S Kumar, F Arfuso, P Newsholme, A Dharmarajan
This study investigated molecular signals essential to sustain cancer stem cells (CSCs) and assessed their activity in the presence of secreted frizzled-related protein 4 (sFRP4) alone or in combination with chemotherapeutic drugs. SFRP4 is a known Wnt antagonist, and is also pro-apoptotic and anti-angiogenic. Additionally, sFRP4 has been demonstrated to confer chemo-sensitization and improve chemotherapeutic efficacy. CSCs were isolated from breast, prostate, and ovary tumor cell lines, and characterized using tumor-specific markers such as CD44(+)/CD24(-)/CD133(+)...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536031/lactate-induces-osteoblast-differentiation-by-stabilization-of-hif1%C3%AE
#10
Yu Wu, Miaomiao Wang, Haihua Feng, Ying Peng, Jieyun Sun, Xiuxia Qu, Chunping Li
Aerobic glycolysis is involved in osteoblast differentiation induced by Wnt signaling or PTH treatment. However, it is still unclear whether lactate, the end product of aerobic glycolysis, plays any role in osteoblast differentiation. Herein we report that in cultures of osteoblast-lineage cells, lactate promoted alkaline phosphatase-positive cell formation, increased the activity of alkaline phosphatase, and induced the expression of osteocalcin. This osteoblast differentiation-inducing effect of lactate can be inhibited by blocking its entry into cells with MCT1 siRNA or inhibitors, and by interfering with its metabolism by using specific siRNAs for LDHB and PDH...
May 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28536011/tg737-regulates-epithelial-mesenchymal-transition-and-cancer-stem-cell-properties-via-a-negative-feedback-circuit-between-snail-and-hnf4%C3%AE-during-liver-stem-cell-malignant-transformation
#11
Qike Huang, Meng Pu, Ge Zhao, Bin Dai, Zhenyuan Bian, Haili Tang, Chong Chen, Wei Liu, Xuan Qu, Liangliang Shen, Kaishan Tao
Determining the origin of liver cancer stem cells is important for treating hepatocellular carcinoma. Tg737 deficiency plays an important role in the malignant transformation of liver stem cells, but the underlying mechanism remains unclear. Here we established a chemical-induced mouse hepatoma model and found that Tg737 and hepatocyte nuclear factor 4-alpha (HNF4α) expression decreased and epithelial-mesenchymal transition (EMT)-related marker expression increased during liver cancer development. To investigate the underlying mechanism, we knocked down Tg737 in WB-F344 (WB) rat hepatic oval cells...
May 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28535514/mir-129-5p-inhibits-proliferation-and-invasion-of-chondrosarcoma-cells-by-regulating-sox4-wnt-%C3%AE-catenin-signaling-pathway
#12
Peng Zhang, Jifeng Li, Yuze Song, Xiao Wang
BACKGROUND/AIMS: Recently, microRNAs (miRNA) have been identified as novel regulators in Chondrosarcoma (CHS). This study was aimed to identify the roles of miR-129-5p-5p in regulation of SOX4 and Wnt/β-catenin signaling pathway, as well as cell proliferation and apoptosis in chondrosarcomas. MATERIALS AND METHODS: Tissue samples were obtained from chondrosarcoma patients. Immunohistochemistry, real-time quantitative RT-PCR (RT-qPCR) and western blot analysis were performed to detect the expressions of miR-129-5p and SOX4...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535511/capn4-enhances-osteopontin-expression-through-activation-of-the-wnt-%C3%AE-catenin-pathway-to-promote-epithelial-ovarian-carcinoma-metastasis
#13
Xiaoming Yang, Jing Sun, Dandan Xia, Xupei Can, Lei Liu, Jing Zhang, Huali Xu, Na Du, Wenxue Liu, Fangqian Shen, Zhenbo Zhang, Yunyan Sun, Xiaowei Xi
BACKGROUND AND AIM: Increasing evidence shows that the calpain regulatory subunit Capn4 can modulate the proliferation and metastasis of cancer cells, and plays an important role in the development of malignant tumors. However, there is no information on the clinical significance of Capn4 in epithelial ovarian carcinoma (EOC) or the molecular mechanisms by which Capn4 promotes the growth and metastasis of EOC. Therefore, the aim of this study was to clarify the role of Capn4 in EOC. METHODS: We evaluated Capn4 and osteopontin (OPN) expression in EOC cell lines and tissues from patients with ovarian cancer by western blotting and immunohistochemical analysis...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534995/low%C3%A2-level-mechanical-vibration-enhances-osteoblastogenesis-via-a-canonical-wnt-signaling%C3%A2-associated-mechanism
#14
Heqi Gao, Mingming Zhai, Pan Wang, Xuhui Zhang, Jing Cai, Xiaofei Chen, Guanghao Shen, Erping Luo, Da Jing
Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534940/the-wnt-regulator-sfrp4-inhibits-mesothelioma-cell-proliferation-migration-and-antagonizes-wnt3a-via-its-netrin-like-domain
#15
Vanathi Perumal, Arun M Dharmarajan, Simon A Fox
Secreted frizzled related proteins (SFRPs) are a family of Wnt regulators which are frequently downregulated in cancers. In malignant mesothelioma (MM), downregulation of SFRP4 has been reported as a mechanism which contributes to aberrant activation of oncogenic Wnt signaling. Here we investigated the biological consequences of SFRP4 in two mesothelioma cell models where this protein is downregulated. We used recombinant SFRP4 and transient overexpression to study changes in proliferation, migration and downstream signaling...
May 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534510/targeting-group-i-p21-activated-kinases-to-control-malignant-peripheral-nerve-sheath-tumor-growth-and-metastasis
#16
G Semenova, D S Stepanova, C Dubyk, E Handorf, S M Deyev, A J Lazar, J Chernoff
Malignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies are available. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, and also the WNT/β-catenin pathway. As Group I p21-activated kinases (Group I Paks, PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533765/leptin-induces-mitosis-and-activates-the-canonical-wnt-%C3%AE-catenin-signaling-pathway-in-neurogenic-regions-of-xenopus-tadpole-brain
#17
Melissa Cui Bender, Christopher J Sifuentes, Robert J Denver
In addition to its well-known role as an adipostat in adult mammals, leptin has diverse physiological and developmental actions in vertebrates. Leptin has been shown to promote development of hypothalamic circuits and to induce mitosis in different brain areas of mammals. We investigated the ontogeny of leptin mRNA, leptin actions on cell proliferation in the brain, and gene expression in the preoptic area/hypothalamus of tadpoles of Xenopus laevis. The level of leptin mRNA was low in premetamorphic tadpoles, but increased strongly at the beginning of metamorphosis and peaked at metamorphic climax...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28533339/structure-based-prediction-of-wnt-binding-affinities-for-frizzled-type-cysteine-rich-domain
#18
Mark Agostino, Sebastian Öther-Gee Pohl, Arunasalam Dharmarajan
Wnt signaling pathways are of significant interest in development and oncogenesis. The first step in these pathways typically involves the binding of a Wnt protein to the cysteine-rich domain (CRD) of a Frizzled receptor; Wnt-Frizzled interactions can be antagonized by secreted Frizzled-related proteins (sFRPs), which also contain a Frizzled-like CRD. The large number of Wnts, Frizzleds and sFRPs, as well as the hydrophobic nature of Wnt, pose challenges to laboratory-based investigations of interactions involving Wnt...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28532855/long-term-influence-of-prenatal-high-sucrose-intake-on-learning-and-memory-of-aged-rat-offspring-with-oxidative-stress-and-disruptions-in-nmdars-wnt-signaling-in-hippocampus
#19
Axin He, Yingying Zhang, Lingjun Li, Xueqin Feng, Bin Wei, Di Zhu, Yanping Liu, Lei Wu, Lubo Zhang, Zhice Xu, Miao Sun
Maternal over-nutrition may increase risks of various diseases in the offspring. Our recent work demonstrated that prenatal high sucrose (HS) could impair spatial acquisitionin the adolescentoffspringrats. This study investigated whether prenatal HS has a long-term impact on cognitive capabilities in the aged offspring rats. The aged HS offspring showed impaired glucose tolerance, significantly increased fasting insulin and insulin resistance index, with unchanged plasma glucose. In the navigation test, the aged HS offspring exhibited longer escape latency and longer swimming path length to the platform...
May 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#20
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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