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https://www.readbyqxmd.com/read/29786110/multi%C3%A2-layered-prevention-and-treatment-of-chronic-inflammation-organ-fibrosis-and-cancer-associated-with-canonical-wnt-%C3%AE-%C3%A2-catenin-signaling-activation-review
#1
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786092/mapping-the-physical-network-of-cellular-interactions
#2
Jean-Charles Boisset, Judith Vivié, Dominic Grün, Mauro J Muraro, Anna Lyubimova, Alexander van Oudenaarden
A cell's function is influenced by the environment, or niche, in which it resides. Studies of niches usually require assumptions about the cell types present, which impedes the discovery of new cell types or interactions. Here we describe ProximID, an approach for building a cellular network based on physical cell interaction and single-cell mRNA sequencing, and show that it can be used to discover new preferential cellular interactions without prior knowledge of component cell types. ProximID found specific interactions between megakaryocytes and mature neutrophils and between plasma cells and myeloblasts and/or promyelocytes (precursors of neutrophils) in mouse bone marrow, and it identified a Tac1+ enteroendocrine cell-Lgr5+ stem cell interaction in small intestine crypts...
May 21, 2018: Nature Methods
https://www.readbyqxmd.com/read/29783855/iec-specific-igf1-promotes-the-expansion-of-intestinal-stem-cells-during-epithelial-regeneration-and-functions-on-the-intestinal-immune-homeostasis
#3
Yu Zheng, Yongli Song, Qi Han, Wenjie Liu, Jiuzhi Xu, Zhengquan Yu, Ran Zhang, Ning Li
It is well known that insulin-like growth factor 1 (IGF1) acts as a trophic factor in small intestine under both physiological and pathophysiological conditions. However, it still lacks direct in vivo evidence of the functions of intestinal epithelial cells (IECs)-specific IGF1 under both normal and pathological conditions. Using IEC-specific IGF1-knockout (cKO) mice and Lgr5-eGFP-CreERT mice, we demonstrate that IEC-specific IGF1 can enhance nutrient uptake, reduce protein catabolism and energy consumption, and promotes the proliferation and expansion of intestinal epithelial cells, including ISCs and intestinal secretory cells...
May 21, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29777575/lgr5-promotes-epithelial-ovarian-cancer-proliferation-metastasis-and-epithelial-mesenchymal-transition-through-the-notch1-signaling-pathway
#4
Wenxue Liu, Jing Zhang, Xupei Gan, Fangqian Shen, Xiaoming Yang, Na Du, Dandan Xia, Lei Liu, Lianqiao Qiao, Jufang Pan, Yunyan Sun, Xiaowei Xi
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) plays a vital role in the development of malignant tumors; however, its biological role and underlying mechanism in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to investigate the biological function and clinical significance of LGR5 in human EOC. We evaluated LGR5 expression in EOC cell lines and tissues from ovarian cancer patients by qPCR, Western blotting, and immunohistochemical analysis. Cell proliferation, colony formation, transwell invasion assay, and scratch-wound assays were conducted to evaluate the expansion and invasion abilities of EOC cells...
May 18, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29774633/a-simple-and-cost-efficient-adherent-culture-platform-for-human-gastric-primary-cells-as-an-in-vitro-model-for-helicobacter-pylori-infection
#5
Samaneh Saberi, Behshad Pournasr, Zahra Farzaneh, Maryam Esmaeili, Mahmoud Eshagh Hosseini, Hossein Baharvand, Marjan Mohammadi
BACKGROUND: Most two- dimensional in vitro models for studying host- H. pylori interactions rely on tumor-derived cell lines, which harbor malignant alterations. The recent development of human gastric organoids has overcome this limitation and provides a highly sophisticated, yet costly, short-term model for H. pylori infection, with restricted use in low-budget centers. METHOD: Tissue specimens from upper, middle, and lower stomachs of H. pylori-negative volunteers were collectively dispersed and cultured on mouse embryonic fibroblast (MEF) or collagen-coated plates...
May 17, 2018: Helicobacter
https://www.readbyqxmd.com/read/29769720/rspo2-inhibition-of-rnf43-and-znrf3-governs-limb-development-independently-of-lgr4-5-6
#6
Emmanuelle Szenker-Ravi, Umut Altunoglu, Marc Leushacke, Célia Bosso-Lefèvre, Muznah Khatoo, Hong Thi Tran, Thomas Naert, Rivka Noelanders, Amin Hajamohideen, Claire Beneteau, Sergio B de Sousa, Birsen Karaman, Xenia Latypova, Seher Başaran, Esra Börklü Yücel, Thong Teck Tan, Lena Vlaeminck, Shalini S Nayak, Anju Shukla, Katta Mohan Girisha, Cédric Le Caignec, Natalia Soshnikova, Zehra Oya Uyguner, Kris Vleminckx, Nick Barker, Hülya Kayserili, Bruno Reversade
The four R-spondin secreted ligands (RSPO1-RSPO4) act via their cognate LGR4, LGR5 and LGR6 receptors to amplify WNT signalling1-3 . Here we report an allelic series of recessive RSPO2 mutations in humans that cause tetra-amelia syndrome, which is characterized by lung aplasia and a total absence of the four limbs. Functional studies revealed impaired binding to the LGR4/5/6 receptors and the RNF43 and ZNRF3 transmembrane ligases, and reduced WNT potentiation, which correlated with allele severity. Unexpectedly, however, the triple and ubiquitous knockout of Lgr4, Lgr5 and Lgr6 in mice did not recapitulate the known Rspo2 or Rspo3 loss-of-function phenotypes...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29760650/characterization-of-wnt-and-notch-responsive-lgr5-hair-cell-progenitors-in-the-striolar-region-of-the-neonatal-mouse-utricle
#7
Dan You, Luo Guo, Wenyan Li, Shan Sun, Yan Chen, Renjie Chai, Huawei Li
Dysfunctions in hearing and balance are largely connected with hair cell (HC) loss. Although regeneration of HCs in the adult cochlea does not occur, there is still limited capacity for HC regeneration in the mammalian utricle from a distinct population of supporting cells (SCs). In response to HC damage, these Lgr5+ SCs, especially those in the striolar region, can regenerate HCs. In this study, we isolated Lgr5+ SCs and Plp1+ SCs (which originate from the striolar and extrastriolar regions, respectively) from transgenic mice by flow cytometry so as to compare the properties of these two subsets of SCs...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29752411/differential-activities-and-mechanisms-of-the-four-r-spondins-in-potentiating-wnt-%C3%AE-catenin-signaling
#8
Soohyun Park, Jie Cui, Wangsheng A Yu, Ling Wu, Kendra Carmon, Qingyun J Liu
The four R-spondins (RSPO1-4) strongly potentiate Wnt signaling and play critical roles in normal development, adult stem cell survival, and cancer development and aggressiveness. All four RSPOs have been suggested to potentiate Wnt signaling by binding to three related receptors, i.e., leucine-rich repeat containing, G protein-coupled receptors 4, 5 and 6 (LGR4/5/6), and then inducing the clearance of two E3 ubiquitin ligases (RNF43 and ZNRF3) that otherwise would ubiquitinate Wnt receptors for degradation...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29726283/lactobacillus-plantarum-is-10506-activates-intestinal-stem-cells-in-a-rodent-model
#9
A F Athiyyah, A Darma, R Ranuh, W Riawan, A Endaryanto, F A Rantam, I S Surono, S M Sudarmo
This study investigated the probiotic effect of Lactobacillus plantarum IS-10506 in activating and regenerating leucine-rich repeat-containing G-protein-coupled receptor (Lgr)5- and B lymphoma Moloney murine leukaemia virus insertion region (Bmi)1-expressing intestinal stem cells in rodents following Escherichia coli serotype 055:B5 lipopolysaccharide (LPS) exposure. Male Sprague-Dawley rats (n=64) were randomised into control (KN), LPS (KL), probiotic + LPS (KL-Pr), and sequential probiotic + LPS + probiotic (KPR-7L) groups...
May 4, 2018: Beneficial Microbes
https://www.readbyqxmd.com/read/29718672/evaluation-of-anti-lgr5-antibodies-by-immunopet-for-imaging-colorectal-tumors-and-development-of-antibody-drug-conjugates
#10
Ali Azhdarinia, Julie Voss, Sukhen C Ghosh, Jo A Simien, Servando Hernandez Vargas, Jie Cui, Wangsheng A Yu, Qingyun Liu, Kendra S Carmon
Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is highly expressed in colorectal tumors and marks colon cancer stem cells that drive tumor growth and metastasis. Recently, we showed that LGR5 is a promising target for antibody-drug conjugate (ADC) therapy. However, it is important to identify LGR5-positive tumors that would respond ADC treatment. Prior to drug conjugation, we evaluated two different anti-LGR5 monoclonal antibodies (mAbs), 8F2 and 9G5, using 89Zr-immunoPET to select the optimal mAb for ADC development and tumor imaging...
May 2, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29713667/the-novel-role-of-lgr5-as-a-regulator-of-cell-homeostasis-and-disease-of-the-gastric-oxyntic-mucosa
#11
EDITORIAL
Yana Zavros
No abstract text is available yet for this article.
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29704302/familial-autosomal-dominant-severe-ankyloglossia-with-tooth-abnormalities
#12
Anaëlle Lenormand, Roman Khonsari, Pierre Corre, Jean Philippe Perrin, Cécile Boscher, Mathilde Nizon, Olivier Pichon, Albert David, Cedric Le Caignec, Helios Bertin, Bertrand Isidor
Ankyloglossia is a congenital oral anomaly characterized by the presence of a hypertrophic and short lingual frenulum. Mutations in the gene encoding the transcription factor TBX22 have been involved in isolated ankyloglossia and X-linked cleft palate. The knockout of Lgr5 in mice results in ankyloglossia. Here, we report a five-generation family including patients with severe ankyloglossia and missing lower central incisors. Two members of this family also exhibited congenital anorectal malformations. In this report, male-to-male transmission was in favor of an autosomal dominant inheritance, which allowed us to exclude the X-linked TBX22 gene...
April 28, 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29695632/selective-targeting-and-eradication-of-lgr5-cscs-using-rspo-conjugated-doxorubicin-liposomes
#13
Jing Cao, Chong Li, Xiaohui Wei, Meiqing Tu, Yan Zhang, Fengwei Xu, Yuhong Xu
Cancer stem cells (CSCs) that may account for only a small fraction of tumor mass were found to play crucial roles during tumor initiating, progression and metastasis. However, they are usually difficult to be treated and notoriously resilient to drug eradication. In this study we aimed at the Wnt signaling characteristic of cancer stem cells and designed a liposomal drug delivery system to target CSCs. Liposomes decorated with RSPO1 on the surface were constructed for specific interactions with the Wnt pathway co-receptor LGR5...
April 25, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29689047/nanogp8-is-the-key-regulator-of-stemness-emt-wnt-pathway-chemoresistance-and-other-malignant-phenotypes-in-gastric-cancer-cells
#14
Xia Ma, Bei Wang, Xiaofang Wang, Yujiao Luo, Wufang Fan
BACKGROUND: Accumulating evidence demonstrated that NANOG1, the key transcription factor for embryonic stem cells, is associated with human cancers. NANOGP8, one of the pseudogenes in NANOG gene family, contains an intact open reading frame and also said to be expressed in cancer tissues. Therefore, a systematic study is greatly needed to address the following questions: among NANOG1 and NANOGP8, which gene is the main contributor for NANOG expression in cancer cells and which one is the key regulator responsible for stemness, epithelial-mesenchymal transition (EMT), metastasis, chemoresistance and other malignant phenotypes...
2018: PloS One
https://www.readbyqxmd.com/read/29675451/cftr-modulates-wnt-%C3%AE-catenin-signaling-and-stem-cell-proliferation-in-murine-intestine
#15
Ashlee M Strubberg, Jinghua Liu, Nancy M Walker, Casey D Stefanski, R John MacLeod, Scott T Magness, Lane L Clarke
Background & Aims: Cystic fibrosis (CF) patients and CF mouse models have increased risk for gastrointestinal tumors. CF mice show augmented intestinal proliferation of unknown etiology and an altered intestinal environment. We examined the role of the cystic fibrosis transmembrane conductance regulator (Cftr) in Wnt/β-catenin signaling, stem cell proliferation, and its functional expression in the active intestinal stem cell (ISC) population. Dysregulation of intracellular pH (pHi ) in CF ISCs was investigated for facilitation of Wnt/β-catenin signaling...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29664186/notch-signaling-regulates-lgr5-olfactory-epithelium-progenitor-stem-cell-turnover-and-mediates-recovery-of-lesioned-olfactory-epithelium-in-mouse-model
#16
Qi Dai, Chen Duan, Wenwen Ren, Fangqi Li, Qian Zheng, Li Wang, Wenyan Li, Xiaoling Lu, Wenli Ni, Yanping Zhang, Yan Chen, Tieqiao Wen, Yiqun Yu, Hongmeng Yu
The Notch signaling pathway regulates stem cell proliferation and differentiation in multiple tissues and organs, and is required for tissue maintenance. However, the role of Notch in regulation of olfactory epithelium (OE) progenitor/stem cells to maintain tissue function is still not clear. A recent study reported that leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is expressed in globose basal cells (GBCs) localized in OE. Through lineage tracing in vivo, we found that Lgr5+ cells act as progenitor/stem cells in OE...
April 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29660380/jade-family-phd-finger-3-jade3-increases-cancer-stem-cell-like-properties-and-tumorigenicity-in-colon-cancer
#17
Yunting Jian, Meng Wang, Yan Zhang, Ruizhang Ou, Ziyuan Zhu, Yangying Ou, Xiangfu Chen, Xin Liang, Yanqing Ding, Libing Song, Xuehu Xu, Wenting Liao
Jade family PHD finger 3 (JADE3) plays a role in inducing histone acetylation during transcription, and is involved in the progression of several human cancers; however, its role in colon cancer remains unclear. Herein, we found that JADE3 was markedly upregulated in colon cancer tissues and significantly correlated with cancer progression, and predicted shorter patient survival. Further, JADE3 was expressed much higher in colon cancer cell lines that are enriched with a stem-like signature. Overexpression of JADE3 increased, while silencing JADE3 reduced cancer stem cell-like traits in colon cancer cells in vitro and in vivo...
April 13, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29648645/does-human-endometrial-lgr5-gene-expression-suggest-the-existence-of-another-hormonally-regulated-epithelial-stem-cell-niche
#18
N Tempest, A M Baker, N A Wright, D K Hapangama
STUDY QUESTION: Is human endometrial leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) gene expression limited to the postulated epithelial stem cell niche, stratum basalis glands, and is it hormonally regulated? SUMMARY ANSWER: LGR5 expressing cells are not limited to the postulated stem cell niche but LGR5 expression is hormonally regulated. WHAT IS KNOWN ALREADY: The human endometrium is a highly regenerative tissue; however, endometrial epithelial stem cell markers are yet to be confirmed...
April 10, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29643507/an-evolutionarily-conserved-ribosome-rescue-pathway-maintains-epidermal-homeostasis
#19
Kifayathullah Liakath-Ali, Eric W Mills, Inês Sequeira, Beate M Lichtenberger, Angela Oliveira Pisco, Kalle H Sipilä, Ajay Mishra, Harunori Yoshikawa, Colin Chih-Chien Wu, Tony Ly, Angus I Lamond, Ibrahim M Adham, Rachel Green, Fiona M Watt
Ribosome-associated mRNA quality control mechanisms ensure the fidelity of protein translation1,2 . Although these mechanisms have been extensively studied in yeast, little is known about their role in mammalian tissues, despite emerging evidence that stem cell fate is controlled by translational mechanisms3,4 . One evolutionarily conserved component of the quality control machinery, Dom34 (in higher eukaryotes known as Pelota (Pelo)), rescues stalled ribosomes 5 . Here we show that Pelo is required for mammalian epidermal homeostasis...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29629872/radical-and-lunatic-fringes-modulate-notch-ligands-to-support-mammalian-intestinal-homeostasis
#20
Preetish Kadur Lakshminarasimha Murthy, Tara Srinivasan, Matthew S Bochter, Rui Xi, Anastasia Kristine Varanko, Kuei-Ling Tung, Fatih Semerci, Keli Xu, Mirjana Maletic-Savatic, Susan E Cole, Xiling Shen
Notch signalling maintains stem cell regeneration at the mouse intestinal crypt base and balances the absorptive and secretory lineages in the upper crypt and villus. Here we report the role of Fringe family of glycosyltransferases in modulating Notch activity in the two compartments. At the crypt base, RFNG is enriched in the Paneth cells and increases cell surface expression of DLL1 and DLL4. This promotes Notch activity in the neighbouring Lgr5 + stem cells assisting their self-renewal. Expressed by various secretory cells in the upper crypt and villus, LFNG promotes DLL surface expression and suppresses the secretory lineage ...
April 9, 2018: ELife
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