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https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#1
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444861/lncrna-malat1-is-dysregulated-in-diabetic-nephropathy-and-involved-in-high-glucose-induced-podocyte-injury-via-its-interplay-with-%C3%AE-catenin
#2
Mengsi Hu, Rong Wang, Xiaobing Li, Minghua Fan, Jiangong Lin, Junhui Zhen, Liqun Chen, Zhimei Lv
Metastasis associated lung adenocarcinoma transcript 1(MALAT1) is a long non-coding RNA, broadly expressed in mammalian tissues including kidney and up-regulated in a variety of cancer cells. To date, its functions in podocytes are largely unknown. β-catenin is a key mediator in the canonical and non-canonical Wnt signalling pathway; its aberrant expression promotes podocyte malfunction and albuminuria, and contributes to kidney fibrosis. In this study, we found that MALAT1 levels were increased in kidney cortices from C57BL/6 mice with streptozocin (STZ)-induced diabetic nephropathy, and dynamically regulated in cultured mouse podocytes stimulated with high glucose, which showed a trend from rise to decline...
April 26, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28435121/proteome-analysis-of-human-embryonic-stem-cells-organelles
#3
Faezeh Shekari, Hossein Nezari, Mehran Rezaei Larijani, Chia-Li Han, Hossein Baharvand, Yu-Ju Chen, Ghasem Hosseini Salekdeh
As the functions of proteins are associated with their cellular localization, the comprehensive sub-cellular proteome knowledge of human embryonic stem cells (hESCs) is indispensable for ensuring a therapeutic effect. Here, we have utilized a sub-cellular proteomics approach to analyze the localization of proteins in the nucleus, mitochondria, crude membrane, cytoplasm, heavy and light microsomes. Out of 2002 reproducibly identified proteins, we detected 762 proteins in a single organelle whereas 160 proteins were found in all sub-cellular fractions...
April 20, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28435069/age-related-increase-in-wnt-inhibitor-causes-a-senescence-like-phenotype-in-human-cardiac-stem-cells
#4
Tamami Nakamura, Tohru Hosoyamaa, Junichi Murakami, Makoto Samura, Koji Ueno, Hiroshi Kurazumi, Ryo Suzuki, Akihito Mikamo, Kimikazu Hamano
Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and leads to unsatisfactory outcomes of cell-based therapies. As the precise mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies for elderly patients with heart failure is severely delayed. In this study, we used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the postnatal heart, to identify secreted factor(s) associated with CSC aging. Human CDCs were isolated from heart failure patients of various ages (2-83 years old)...
April 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431267/mir-19-targeting-of-gsk3%C3%AE-mediates-sulforaphane-suppression-of-lung-cancer-stem-cells
#5
Jianyun Zhu, Shijia Wang, Yue Chen, Xiaoting Li, Ye Jiang, Xue Yang, Yuan Li, Xiaoqian Wang, Yu Meng, Mingming Zhu, Xiao Ma, Cong Huang, Rui Wu, Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Hongyu Han
Cancer stem cells (CSCs) play a central role in the development of cancer. The canonical Wnt/β-catenin pathway is critical for maintaining stemness of CSCs. Phytochemicals from dietary compounds possess anti-CSCs properties and have been characterized as promising therapeutic agents for the prevention and treatment of many cancers. To date, the involvement and function of miR-19, a key oncogenic miRNA, in regulating Wnt/β-catenin pathway and lung CSCs has not been defined. Meanwhile, the effect of sulforaphane (SFN) on lung CSCs also remains to be elucidated...
April 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28429652/atypical-regulators-of-wnt-%C3%AE-catenin-signaling-as-potential-therapeutic-targets-in-hepatocellular-carcinoma
#6
Jianxiang Chen, Muthukumar Rajasekaran, Kam M Hui
Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. Hepatocellular carcinoma development depends on the inhibition and activation of multiple vital pathways, including the Wnt signaling pathway. The Wnt/β-catenin pathway lies at the center of various signaling pathways that regulate embryonic development, tissue homeostasis and cancers. Activation of the Wnt/β-catenin pathway has been observed frequently in hepatocellular carcinoma. However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28427856/frizzled-3-acts-upstream-of-alcam-during-embryonic-eye-development
#7
Franziska A Seigfried, Wiebke Cizelsky, Astrid S Pfister, Petra Dietmann, Paul Walther, Michael Kühl, Susanne J Kühl
Formation of a functional eye during vertebrate embryogenesis requires different processes such as cell migration, cell-cell interactions as well as intracellular signalling processes. It was previously shown that the non-canonical Wnt receptor Frizzled 3 (Fzd3) is required for proper eye formation, however, the underlying mechanism is poorly understood. Here we demonstrate that loss of Fzd3 induces severe malformations of the developing eye and that this defect is phenocopied by loss of the activated leukocyte cell adhesion molecule (Alcam)...
April 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28423716/oncogenic-features-of-neuromedin-u-in-breast-cancer-are-associated-with-nmur2-expression-involving-crosstalk-with-members-of-the-wnt-signaling-pathway
#8
Stefan Garczyk, Natalie Klotz, Sabrina Szczepanski, Bernd Denecke, Wiebke Antonopoulos, Saskia von Stillfried, Ruth Knüchel, Michael Rose, Edgar Dahl
Neuromedin U (NMU) has been shown driving the progression of various tumor entities, including breast cancer. However, the expression pattern of NMU and its receptors in breast cancer tissues as well as systematic insight into mechanisms and downstream targets of the NMU-driven signaling pathways are still elusive. Here, NMU expression was found up-regulated in all breast cancer subtypes when compared to healthy breast tissue. Using an in silico dataset comprising 1,195 samples, high NMU expression was identified as an indicator of poor outcome in breast tumors showing strong NMUR2 expression...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420671/ptk7-localization-and-protein-stability-is-affected-by-canonical-wnt-ligands
#9
Hanna Berger, Marlen Breuer, Hanna Peradziryi, Martina Podleschny, Ralf Jacob, Annette Borchers
PTK7 (protein tyrosine kinase 7) is an evolutionarily conserved transmembrane receptor with important roles in embryonic development and disease. Originally identified as a gene upregulated in colon cancer it was later shown to regulate planar cell polarity (PCP) and directional cell movement. PTK7 is a Wnt co-receptor, however its role in Wnt signaling remains controversial. Here, we find evidence that place PTK7 at the intersection of canonical and non-canonical Wnt signaling pathways. In presence of canonical Wnt ligands PTK7 is subject to caveolin-mediated endocytosis, while it is unaffected by non-canonical Wnt ligands...
April 18, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28418865/anti-helminthic-niclosamide-inhibits-ras-driven-oncogenic-transformation-via-activation-of-gsk-3
#10
Sung Yong Ahn, Ji Hye Yang, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Jun Seop Yun, Hee Eun Kang, Yoonmi Lee, Jiwon Choi, Hyun Sil Kim, Jong In Yook
Despite the importance of Ras oncogenes as a therapeutic target in human cancer, their 'undruggable' tertiary structures limit the effectiveness of anti-Ras drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent degradation. In the accompanying report, we show that the anti-helminthic niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer cells, with reversion of Snail-mediated epithelial-mesenchymal transition...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418862/niclosamide-is-a-potential-therapeutic-for-familial-adenomatosis-polyposis-by-disrupting-axin-gsk3-interaction
#11
Sung Yong Ahn, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Ji Hye Yang, So Young Cha, Eunae Sandra Cho, Yoonmi Lee, Jeong Seok Cha, Hyun Soo Cho, Yoon Jeon, Young-Su Yuk, Suebean Cho, Kyoung Tai No, Hyun Sil Kim, Ho Lee, Jiwon Choi, Jong In Yook
The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling and EMT comprises an attractive therapeutic strategy, molecular targets for small molecules reverting Wnt and EMT have not been widely studied. Meanwhile, the anti-helminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418602/expression-of-low-density-lipoprotein-related-receptors-5-and-6-lrp5-6-in-psoriasis-skin
#12
Albert Duvetorp, Renate Slind Olsen, Helena Nyström, Marita Skarstedt, Olaf Dienus, Ulrich Mrowietz, Jan Söderman, Oliver Seifert
Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signaling. Wnt ligands are thought to play an important role in innate immunity and psoriasis and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28417011/chemical-biology-reveals-carf-as-a-positive-regulator-of-canonical-wnt-signaling-by-promoting-tcf-%C3%AE-catenin-transcriptional-activity
#13
Xiaoli He, Wenjuan Zhang, Chen Yan, Fen Nie, Chen Li, Xiaofen Liu, Cong Fei, Shengdi Li, Xiaomin Song, Yingying Jia, Rong Zeng, Dianqing Wu, Weijun Pan, Xiaojiang Hao, Lin Li
Wnt/β-catenin signaling regulates multiple biological processes and aberration of this pathway is frequently observed in human cancers. Previously, we uncovered NC043 as a small-molecule inhibitor of Wnt/β-catenin signaling. Here, we identified CARF as the cellular target of NC043. We found that NC043 binds directly to CARF through forming a covalent bond with the Cys-516 residue of CARF. Further study revealed that CARF interacts with Dvl, which potentiates the Dvl-c-Jun-β-catenin-TCF transcriptional complex and thus promotes Wnt signaling activation...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28416592/-wnt-er-is-coming-wnt-signalling-in-chronic-lung-diseases
#14
H A Baarsma, M Königshoff
Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD...
April 17, 2017: Thorax
https://www.readbyqxmd.com/read/28416583/physiological-and-pathological-roles-in-human-adrenal-of-the-glomeruli-defining-matrix-protein-npnt-nephronectin
#15
Ada Ee Der Teo, Sumedha Garg, Timothy Isaac Johnson, Wanfeng Zhao, Junhua Zhou, Celso Enrique Gomez-Sanchez, Mark Gurnell, Morris Jonathan Brown
Primary aldosteronism is a common cause of hypertension, which becomes refractory if undiagnosed, but potentially curable when caused by an aldosterone-producing adenoma (APA). The discovery of somatic mutations and differences in clinical presentations led to recognition of small but common zona glomerulosa (ZG)-like adenomas, distinct from classical large zona fasciculata-like adenomas. The inverse correlation between APA size and aldosterone synthase expression prompted us to undertake a systematic study of genotype-phenotype relationships...
April 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28411439/neuropeptide-y-enhances-proliferation-and-prevents-apoptosis-in-rat-bone-marrow-stromal-cells-in-association-with-activation-of-the-wnt-%C3%AE-catenin-pathway-in-vitro
#16
Jianqun Wu, Song Liu, Huan Meng, Tianyu Qu, Su Fu, Zhao Wang, Jianguo Yang, Dan Jin, Bin Yu
Neuropeptide Y (NPY) exhibits a critical but poorly understood regulatory signaling function and has been shown to promote proliferation, vascularization and migration in several types of cells and tissues. However, little is known about the specific role of NPY in the proliferation and apoptosis of bone marrow stromal cells (also known as bone marrow-derived mesenchymal stem cells, BMSCs), which contain a subpopulation of multipotent skeletal stem cells. Based on BrdU incorporation tests, Cell Counting Kit-8, flow cytometry, quantitative polymerase chain reaction and western blotting, we showed that NPY significantly promoted the proliferation of BMSCs in a concentration-dependent manner, with a maximal effect observed at a concentration of 10(-10)M for pro-proliferative and 10(-12)M for anti-apoptotic activities...
April 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28408959/role-of-the-wnt-signaling-molecules-in-the-tooth
#17
REVIEW
Masato Tamura, Eiji Nemoto
Wnt signaling plays a central role in many processes during embryonic development and adult homeostasis. At least 19 types of Wnt ligands, receptors, transducers, transcription factors, and antagonists have been identified in mammals. Two distinct Wnt signaling pathways, the canonical signaling pathway and the noncanonical signaling pathway, have been described. Some Wnt signaling pathway components are expressed in the dental epithelium and mesenchyme during tooth development in humans and mice. Functional studies and experimental analysis of relevant animal models confirm the effects of Wnt signaling pathway on the regulation of developing tooth formation and adult tooth homeostasis...
November 2016: Japanese Dental Science Review
https://www.readbyqxmd.com/read/28405929/thermodynamics-in-cancers-opposing-interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway
#18
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28404920/noncanonical-wnt-signaling-plays-an-important-role-in-modulating-canonical-wnt-regulated-stemness-proliferation-and-terminal-differentiation-of-hepatic-progenitors
#19
Jiaming Fan, Qiang Wei, Junyi Liao, Yulong Zou, Dongzhe Song, Dongmei Xiong, Chao Ma, Xue Hu, Xiangyang Qu, Liqun Chen, Li Li, Yichun Yu, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye Wu, Yi Shu, Jiayan Lei, Yasha Li, Wenwen Zhang, Rex C Haydon, Hue H Luu, Ailong Huang, Tong-Chuan He, Hua Tang
The liver provides vital metabolic, exocrine and endocrine functions in the body as such pathological conditions of the liver lead to high morbidity and mortality. The liver is highly regenerative and contains facultative stem cells that become activated during injury to replicate to fully recover mass and function. Canonical Wnt/β-catenin signaling plays an important role in regulating the proliferation and differentiation of liver progenitor cells during liver regeneration. However, possible roles of noncanonical Wnts in liver development and regeneration remain undefined...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402679/inhibition-of-osteogenesis-surrounding-the-titanium-implant-by-cgrp-deficiency
#20
Yao Liu, Guangsen Zheng, Li Liu, Zhi Wang, Yiyao Wang, Qianming Chen, En Luo
Previous studies have suggested one of neurotransmitters, calcitonin gene-related peptide (CGRP), modulates local regulation of bone metabolism; however, the regulating signaling pathway is still being explored. The objective of this study was to determine whether CGRP deficiency affects the osteogenesis surrounding titanium implants in vivo. Titanium screws were implanted in 72 adult rats, which were divided into three groups randomly: Sham, inferior alveolar neurectomy (IAN), and IAN+CGRP. Saline solution containing CGRP (concentration: 100 nmol/L) was injected into the area surrounding the implants in the IAN+CGRP group every day post operation...
April 12, 2017: Connective Tissue Research
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