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https://www.readbyqxmd.com/read/28521288/hypermethylation-of-ndn-promotes-cell-proliferation-by-activating-the-wnt-signaling-pathway-in-colorectal-cancer
#1
Yu-Han Hu, Qing Chen, Yan-Xia Lu, Jian-Ming Zhang, Chun Lin, Fan Zhang, Wen-Juan Zhang, Xiao-Min Li, Wei Zhang, Xue-Nong Li
The progression of CRC is a multistep process involving several genetic changes or epigenetic modifications. NDN is a member of the MAGE family, encoding a protein that generally suppresses cell proliferation and acting as a transcriptional repressor. Immunohistochemical staining revealed that the expression of NDN was significantly down-regulated in CRC tissues compared with normal tissues and the down-regulation of NDN in CRC could reflect the hypermethylation of the NDN promoter. Treatment of the CRC cell line SW480 with the demethylating agent 5-Aza-CdR restored the NDN expression level...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515679/downregulation-of-the-repressor-element-1-silencing-transcription-factor-rest-is-associated-with-akt-mtor-and-wnt-%C3%AE-catenin-signaling-in-prion-diseases-models
#2
Zhiqi Song, Syed Z A Shah, Wei Yang, Haodi Dong, Lifeng Yang, Xiangmei Zhou, Deming Zhao
Prion diseases are a group of infectious diseases characterized by multiple neuropathological changes, yet the mechanisms that preserve function and protect against prion-associated neurodegeneration are still unclear. We previously reported that the repressor element 1-silencing transcription factor (REST) alleviates neurotoxic prion peptide (PrP106-126)-induced toxicity in primary neurons. Here we confirmed the findings of the in vitro model in 263K infected hamsters, an in vivo model of prion diseases and further showed the relationships between REST and related signaling pathways...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28514532/the-dickkopf1-ckap4-axis-creates-a-novel-signaling-pathway-and-may-represent-a-molecular-target-for-cancer-therapy
#3
REVIEW
Akira Kikuchi, Katsumi Fumoto, Hirokazu Kimura
Dickkopf 1 (DKK1) is a secretory protein and antagonizes oncogenic Wnt signaling by binding to the Wnt co-receptor low-density lipoprotein receptor-related proteins 6 (LRP6). DKK1 is also suggested to regulate its own signaling to associate with tumor aggressiveness. However, the underlying mechanism by which DKK1 promotes cancer cell proliferation has remained to be clarified for a long time. It has been recently found that cytoskeleton-associated protein 4 (CKAP4), which was originally reported as an endoplasmic reticulum membrane protein, acts as a novel DKK1 receptor...
May 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28513615/exome-sequencing-of-two-italian-pedigrees-with-non-isolated-chiari-malformation-type-i-reveals-candidate-genes-for-cranio-facial-development
#4
Elisa Merello, Lorenzo Tattini, Alberto Magi, Andrea Accogli, Gianluca Piatelli, Marco Pavanello, Domenico Tortora, Armando Cama, Zoha Kibar, Valeria Capra, Patrizia De Marco
Chiari malformation type I (CMI) is a congenital abnormality of the cranio-cerebral junction with an estimated incidence of 1 in 1280. CMI is characterized by underdevelopment of the occipital bone and posterior fossa (PF) and consequent cerebellar tonsil herniation. The presence for a genetic basis to CMI is supported by many lines of evidence. The cellular and molecular mechanisms leading to CM1 are poorly understood. The occipital bone formation is dependent on complex interactions between genes and molecules with pathologies resulting from disruption of this delicate process...
May 17, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28484252/wnt-inhibitory-factor-1-wif1-methylation-and-its-association-with-clinical-prognosis-in-patients-with-chondrosarcoma
#5
Pei Liu, Jacson K Shen, Francis J Hornicek, Fuyun Liu, Zhenfeng Duan
Chondrosarcoma (CS) is a rare cancer, but it is the second most common primary malignant bone tumor and highly resistant to conventional chemotherapy and radiotherapy. Aberrant DNA methylation in the promoter CpG island of Wnt inhibitory factor 1 (WIF1) has been observed in different cancers. However, no studies have shown the relationship between WIF1 methylation and CS. In this study, we found promoter methylated WIF1 in both CS cell lines (CS-1 and SW1353) and tumor tissues. Western blot analysis confirmed loss WIF1 expression and activation of Wnt pathway proteins (Wnt5a/b, LRP6, and Dvl2)...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28467820/non-equivalence-of-wnt-and-r-spondin-ligands-during-lgr5-intestinal-stem-cell-self-renewal
#6
Kelley S Yan, Claudia Y Janda, Junlei Chang, Grace X Y Zheng, Kathryn A Larkin, Vincent C Luca, Luis A Chia, Amanda T Mah, Arnold Han, Jessica M Terry, Akifumi Ootani, Kelly Roelf, Mark Lee, Jenny Yuan, Xiao Li, Christopher R Bolen, Julie Wilhelmy, Paige S Davies, Hiroo Ueno, Richard J von Furstenberg, Phillip Belgrader, Solongo B Ziraldo, Heather Ordonez, Susan J Henning, Melissa H Wong, Michael P Snyder, Irving L Weissman, Aaron J Hsueh, Tarjei S Mikkelsen, K Christopher Garcia, Calvin J Kuo
The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28467818/surrogate-wnt-agonists-that-phenocopy-canonical-wnt-and-%C3%AE-catenin-signalling
#7
Claudia Y Janda, Luke T Dang, Changjiang You, Junlei Chang, Wim de Lau, Zhendong A Zhong, Kelley S Yan, Owen Marecic, Dirk Siepe, Xingnan Li, James D Moody, Bart O Williams, Hans Clevers, Jacob Piehler, David Baker, Calvin J Kuo, K Christopher Garcia
Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28456913/the-effect-and-osteoblast-signaling-response-of-trace-silicon-doping-hydroxyapatite
#8
Tian Sun, Ming Wang, Yiran Shao, Liping Wang, Yingchun Zhu
It is commonly accepted that silicon-doped hydroxyapatite (HAp) can achieve good repair effects for both spinal fusion and bone defect filling. However, the underlying mechanism by which silicon aids such beneficial effects is still not fully understood. Herein, we report on silicon-doped hydroxyapatites with excellent biocompatibility to osteoblast cells and suggest the signaling pathway involved. Non-doped HAp and trace Si-doped HAp (Si/HAp) with Si concentration close to and higher than natural bones were synthesized (i...
April 29, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28427938/ganoderma-lucidum-reishi-suppresses-proliferation-and-migration-of-breast-cancer-cells-via-inhibiting-wnt-%C3%AE-catenin-signaling
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
Elham Rismani, Mohammad Sadegh Fazeli, Habibollah Mahmoodzadeh, Aghdas Movassagh, 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%C3%A2-cells
#16
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 newborn (postnatal day 0) 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
#17
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
#18
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...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28341812/parkinson-s-disease-associated-receptor-gpr37-is-an-er-chaperone-for-lrp6
#19
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...
May 2017: EMBO Reports
https://www.readbyqxmd.com/read/28341377/lrp5-from-bedside-to-bench-to-bone
#20
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
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