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https://www.readbyqxmd.com/read/28427938/ganoderma-lucidum-reishi-suppresses-proliferation-and-migration-of-breast-cancer-cells-via-inhibiting-wnt-%C3%AE-catenin-signaling
#1
Yu Zhang
The medical mushroom Ganoderma lucidum (Reishi), a traditional Chinese medicine, has exhibited a promising anti-cancer effect. However, the molecular mechanism of its action on cancer cells remains unclear. Aberrant activation of Wnt/β-catenin signaling pathway is the cause of many types of cancer, including breast cancer. Here we investigated the effect of Reishi on Wnt/β-catenin signaling pathway and elucidated the molecular mechanism of its function in inhibiting breast cancer cells. We found that Reishi blocked Wnt/β-catenin signaling through inhibiting the phosphorylation of Wnt co-receptor LRP6...
April 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28425175/haemorrhagic-snake-venom-metalloproteases-and-human-adams-cleave-lrp5-6-which-disrupts-cell-cell-adhesions-in-vitro-and-induces-haemorrhage-in-vivo
#2
Tadahiko Seo, Taketo Sakon, Shiori Nakazawa, Asuka Nishioka, Kohei Watanabe, Kaori Matsumoto, Mari Akasaka, Narumi Shioi, Hitoshi Sawada, Satohiko Araki
Snake venom metalloproteases (SVMPs) are members of the a disintegrin and metalloprotease (ADAM) family of proteins, as they possess similar domains. SVMPs are known to elicit snake venom-induced haemorrhage; however, the target proteins and cleavage sites are not known. In this work, we identified a target protein of vascular apoptosis-inducing protein 1 (VAP1), an SVMP, relevant to its ability to induce haemorrhage. VAP1 disrupted cell-cell adhesions by relocating VE-cadherin and γ-catenin from the cell-cell junction to the cytosol, without inducing proteolysis of VE-cadherin...
April 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28423559/rottlerin-as-a-novel-chemotherapy-agent-for-adrenocortical-carcinoma
#3
Yi Zhu, Minjie Wang, Xu Zhao, Lei Zhang, Yigao Wu, Bangqi Wang, Weilie Hu
Adrenocortical carcinoma (ACC) is a rare, but aggressive endocrine malignancy with a generally poor clinical outcome. There is no effective therapy for advanced and metastatic ACC. In our study, we found that an existing drug (rottlerin) exerted its tumour-suppressive function in ACC. Specifically, rottlerin inhibited cellular proliferation of ACC cell lines (NCI-H295R and SW-13) in a dose- and time-dependent manner. We also found that rottlerin induced cell apoptosis and promoted G0/G1 cell cycle arrest in ACC cell lines...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418856/low-density-lipoprotein-receptor-related-protein-6-is-a-novel-coreceptor-of-protease-activated-receptor-2-in-the-dynamics-of-cancer-associated-%C3%AE-catenin-stabilization
#4
Jeetendra Kumar Nag, Arun Kancharla, Myriam Maoz, Hagit Turm, Daniel Agranovich, Chhedi Lal Gupta, Beatrice Uziely, Rachel Bar-Shavit
Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the molecular machinery of PAR2-instigated tumors remains to be elucidated. We show that PAR2 is a potent inducer of β-catenin stabilization, a core process in cancer biology, leading to its transcriptional activity. Novel association of low-density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds (Fz), with PAR2 takes place following PAR2 activation. The association between PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence resonance energy transfer (BRET), and confocal microscopy analysis...
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
#5
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/28403150/pedf-increases-the-tumoricidal-activity-of-macrophages-towards-prostate-cancer-cells-in-vitro
#6
Dalia Martinez-Marin, Courtney Jarvis, Thomas Nelius, Werner de Riese, Olga V Volpert, Stéphanie Filleur
BACKGROUND: Although inflammation and prostate cancer (PCa) have been linked, the molecular interactions between macrophages and PCa cells are poorly explored. Pigment Epithelium-Derived Factor (PEDF) is an anti-angiogenic and anti-tumor factor. We previously showed that PEDF induces macrophages recruitment in vitro, correlates with macrophages density in human prostate, and stimulates macrophages polarization towards the classically activated pathway. Here, we demonstrate that PEDF modulates the interaction between macrophages and PCa cells through a bidirectional signalling leading to tumor cell apoptosis and phagocytosis...
2017: PloS One
https://www.readbyqxmd.com/read/28387660/pattern-of-lrp6-gene-expression-in-tumoral-tissues-of-colorectal-cancer
#7
Elham Rismani, Mohammad Sadegh Fazeli, Habibollah Mahmoodzadeh, Aghdas Movassgh, Sina Azami, Morteza Karimipoor, Ladan Teimoori-Toolabi
BACKGROUND: Colorectal cancer (CRC) is known as one of the most leading causes of death from cancer in the world. Wnt signaling pathway is the most important signaling pathway activated in this type of cancer. The low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) functions as a co-receptor in order to trigger this signaling pathway. OBJECTIVE: The expression of LRP6 was studied in cell lines, tumoral and normal adjacent tissues from patients affected with colorectal cancer...
March 31, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28359679/activation-of-wnt-signaling-increases-numbers-of-enteric-neurons-derived-from-neonatal-mouse-and-human-progenitors-cells
#8
Ying Zhang, Karin Seid, Florian Obermayr, Lothar Just, Peter H Neckel
BACKGROUND & AIMS: Neural stem and progenitor cells from the enteric nervous system (ENS) might serve as a source of cells for treatment of neurogastrointestinal disorders. Before we can use these cells, we must increase our understanding of the signaling mechanisms that regulate proliferation and differentiation. We systematically evaluated the effects of canonical Wnt signaling on proliferation and differentiation of cultured ENS progenitor cells from neonatal mice and humans. METHODS: We isolated ENS progenitors from tunica muscularis of the small intestine of new-born (P0) wild-type C57BL/6 mice as well as from Wnt1-Cre2 reporter mice...
March 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28351327/nigericin-decreases-the-viability-of-multidrug-resistant-cancer-cells-and-lung-tumorspheres-and-potentiates-the-effects-of-cardiac-glycosides
#9
Juan Sebastian Yakisich, Neelam Azad, Vivek Kaushik, George A O'Doherty, Anand Krishnan V Iyer
Multiple factors including tumor heterogeneity and intrinsic or acquired resistance have been associated with drug resistance in lung cancer. Increased stemness and the plasticity of cancer cells have been identified as important mechanisms of resistance; therefore, treatments targeting cancer cells independent of stemness phenotype would be much more effective in treating lung cancer. In this article, we have characterized the anticancer effects of the antibiotic Nigericin in cells displaying varying degrees of stemness and resistance to anticancer drugs, arising from (1) routine culture conditions, (2) prolonged periods of serum starvation...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28347816/evolutionary-conservation-of-notch-signaling-inhibition-by-tmem131l-overexpression
#10
Sébastien Szuplewski, Nesrine Maharzi, Elisabeth Nelson, Kutaiba Alhaj Hussen, Bernard Mignotte, Isabelle Guénal, Bruno Canque
Human KIAA0922/TMEM131L encodes a transmembrane protein, TMEM131L, that regulates the canonical Wnt/β-catenin signaling pathway by eliciting the lysosome-dependent degradation of phosphorylated LRP6 co-receptor. Here, we use a heterospecific Drosophila transgenic model to examine the potential evolutionary conservation of TMEM131L function. Analysis of TMEM131L transgenic flies shows that TMEM131L interference with the Wnt pathway results primarily from a Notch-dependent decrease in Wingless production. Consistently, lentivirus-mediated overexpression of TMEM131L in human CD34(+) hematopoietic progenitor cells leads to decreased susceptibility to Notch1 ligation and defective commitment toward the T lineage...
March 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28341812/parkinson-s-disease-associated-receptor-gpr37-is-an-er-chaperone-for-lrp6
#11
Birgit S Berger, Sergio P Acebron, Jessica Herbst, Stefan Koch, Christof Niehrs
Wnt/β-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky β-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/β-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis...
March 24, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28341377/lrp5-from-bedside-to-bench-to-bone
#12
Bart O Williams
A role for Low-density lipoprotein related receptor 5 (LRP5) in human bone was first established by the identification of genetic alterations that led to dramatic changes in human bone mass. Shortly thereafter, mutations that altered the function of the Sclerostin (SOST) gene were also associated with altered human bone mass. Subsequent studies of LRP5 and Sclerostin have provided important insights into the mechanisms by which these proteins regulate skeletal homeostasis. Sclerostin normally binds to LRP5 and the related LRP6 protein and prevents their activation by Wnt ligands...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28337300/mutation-of-mir-21-targets-endogenous-lipoprotein-receptor-related-protein-6-and-nonalcoholic-fatty-liver-disease
#13
Chang-Ping Li, Hong-Jue Li, Jiao Nie, Xia Chen, Xian Zhou
Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28299632/transgenic-expression-of-a-canonical-wnt-inhibitor-kallistatin-is-associated-with-decreased-circulating-cd19-b-lymphocytes-in-the-peripheral-blood
#14
Jeffrey D McBride, Xiaochen Liu, William L Berry, Ralf Janknecht, Rui Cheng, Kelu Zhou, Evangelos V Badiavas, Jian-Xing Ma
Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles...
March 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28289266/wnts-synergize-to-activate-%C3%AE-catenin-signaling
#15
Anshula Alok, Zhengdeng Lei, N Suhas Jagannathan, Simran Kaur, Steven G Rozen, Lisa Tucker-Kellogg, David M Virshup
Wnt ligands regulate diverse signaling pathways during development, maintenance of tissue homeostasis, and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed alone, and the consequences of Wnt gene co-expression are not well understood. We studied the effect of co-expression of Wnts on the β-catenin signaling pathway. While some Wnts are deemed 'non-canonical' due to their limited ability to activate β-catenin when expressed alone, unexpectedly, we find that multiple Wnt combinations can synergistically activate β-catenin signaling in multiple cell types...
March 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28273524/altered-bone-microarchitecture-and-gene-expression-profile-due-to-calcium-deficiency-in-a-mouse-model-of-myeloma
#16
Hélène Libouban, Daniel Chappard
It is not clear why patients with an indolent form of multiple myeloma (MM) develop into an aggressive form with poor prognostic. We investigated the effect of a dietary calcium deficiency on tumor growth, osteolysis and gene expression in the 5T2MM murine model. Two groups of C57BL/KaLwRij mice received 5T2MM cells and started a diet with normal (0.8%; "normal-Ca-MM") or low calcium content (0.05%; "low-Ca-MM"). Two control groups (without 5T2MM cells) received either a normal or low calcium diet (normal-Ca and low-Ca groups)...
May 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28267633/sclerostin-stimulates-angiogenesis-in-human-endothelial-cells
#17
Angela Oranger, Giacomina Brunetti, Graziana Colaianni, Roberto Tamma, Claudia Carbone, Luciana Lippo, Giorgio Mori, Paolo Pignataro, Nunzio Cirulli, Roberta Zerlotin, Biagio Moretti, Angela Notarnicola, Domenico Ribatti, Maria Grano, Silvia Colucci
Sclerostin, negative regulator of bone formation, has been originally known as an osteocyte product. Recently, it has been also detected in hypertrophic chondrocytes, distinctive cells of avascular cartilage which is invaded by capillaries and then replaced by vascularized bone. Thus, we hypothesized that sclerostin, in addition to its role already known, may exert an angiogenic activity. We first proved that sclerostin increased the proliferation of human umbilical vein endothelial cells (HUVECs), and next, by using the chicken chorioallantoic membrane (CAM) in vivo assay, we demonstrated that it exerts an angiogenic activity similar to that of vascular endothelial growth factor (VEGF)...
March 3, 2017: Bone
https://www.readbyqxmd.com/read/28247948/role-of-wnt-co-receptor-lrp6-in-triple-negative-breast-cancer-cell-migration-and-invasion
#18
Jinlu Ma, Wenyan Lu, Dongquan Chen, Bo Xu, Yonghe Li
The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential Wnt co-receptor of the Wnt/β-catenin signaling pathway. Although studies have shown an increased expression of LRP6 in several types of cancer, its function in tumor development and progression remains to be elucidated. We herein demonstrated that LRP6 expression is up-regulated in human triple negative breast cancer (TNBC) patients and human TNBC cell lines, and that knockdown of LRP6 expression and treatment of recombinant Mesd protein (a specific inhibitor of LRP6) significantly decreased cell migration and invasion of TNBC MDA-MB-231 and BT549 cells...
March 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230988/design-and-synthesis-of-novel-cyclic-amine-benzimidazoles-for-the-treatment-of-pancreatic-cancer
#19
Vibha Pathak, Corinne Elizabeth Augelli-Szafran, Han-Xun Wei, Yonghe Li, Patsy G Oliver, Wenyan Lu, Donald J Buchsbaum, Mark J Suto
Wnt/beta-Catenin signaling pathway has a very important role in pancreatic ductal adenocarcinoma (PDAC) initiation and progression. This signaling pathway has been implicated in angiogenesis, maintenance of resistant CICs (cancer-initiating cells), metastasis, regulation of cell cycle, apoptosis and chemoresistance. We investigated the activity of a chemical series of phenyl benzimidazoles, small molecule inhibitors of Wnt signaling in LRP6-expressing HEK 293 cells against PDAC cells. Several benzimidazoles were designed, synthesized and screened under adherent and CIC conditions...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28223363/autoinhibition-of-dishevelled-protein-regulated-by-its-extreme-c-terminus-plays-a-distinct-role-in-wnt-%C3%AE-catenin-and-wnt-planar-cell-polarity-pcp-signaling-pathways
#20
Jing Qi, Ho-Jin Lee, Audrey Saquet, Xiao-Ning Cheng, Ming Shao, Jie J Zheng, De-Li Shi
Dishevelled (Dvl) is a key intracellular signaling molecule that mediates the activation of divergent Wnt pathways. It contains three highly conserved domains known as DIX, PDZ, and DEP, the functions of which have been well characterized in β-catenin-dependent canonical and β-catenin-independent noncanonical Wnt signaling. The C-terminal region is also highly conserved from invertebrates to vertebrates. However, its function in regulating the activation of different Wnt signals remains unclear. We reported previously that Dvl conformational change triggered by the highly conserved PDZ-binding C terminus is important for the pathway specificity...
April 7, 2017: Journal of Biological Chemistry
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