keyword
MENU ▼
Read by QxMD icon Read
search

Rspo2

keyword
https://www.readbyqxmd.com/read/29769720/rspo2-inhibition-of-rnf43-and-znrf3-governs-limb-development-independently-of-lgr4-5-6
#1
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/29752411/differential-activities-and-mechanisms-of-the-four-r-spondins-in-potentiating-wnt-%C3%AE-catenin-signaling
#2
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/29505958/wnt-signalling-drives-context-dependent-differentiation-or-proliferation-in-neuroblastoma
#3
Marianna Szemes, Alexander Greenhough, Zsombor Melegh, Sally Malik, Aysen Yuksel, Daniel Catchpoole, Kelli Gallacher, Madhu Kollareddy, Ji Hyun Park, Karim Malik
Neuroblastoma is one of the commonest and deadliest solid tumours of childhood, and is thought to result from disrupted differentiation of the developing sympathoadrenergic lineage of the neural crest. Neuroblastoma exhibits intra- and intertumoural heterogeneity, with high risk tumours characterised by poor differentiation, which can be attributable to MYCN-mediated repression of genes involved in neuronal differentiation. MYCN is known to co-operate with oncogenic signalling pathways such as Alk, Akt and MEK/ERK signalling, and, together with c-MYC has been shown to be activated by Wnt signalling in various tissues...
April 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29405118/r-spondins-can-potentiate-wnt-signaling-without-lgrs
#4
Andres M Lebensohn, Rajat Rohatgi
The WNT signaling pathway regulates patterning and morphogenesis during development and promotes tissue renewal and regeneration in adults. The R-spondin (RSPO) family of four secreted proteins, RSPO1-4, amplifies target cell sensitivity to WNT ligands by increasing WNT receptor levels. Leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4-6 are considered obligate high-affinity receptors for RSPOs. We discovered that RSPO2 and RSPO3, but not RSPO1 or RSPO4, can potentiate WNT/β-catenin signaling in the absence of all three LGRs...
February 6, 2018: ELife
https://www.readbyqxmd.com/read/29383135/upregulation-of-rspo2-gpr48-lgr4-signaling-in-papillary-thyroid-carcinoma-contributes-to-tumor-progression
#5
Yea Eun Kang, Jin-Man Kim, Koon Soon Kim, Joon Young Chang, Mingyu Jung, Junguee Lee, Shinae Yi, Hyeon Woo Kim, Jung Tae Kim, Kyungmin Lee, Min Jeong Choi, Seul Ki Kang, Seong Eun Lee, Hyon-Seung Yi, Bon Seok Koo, Minho Shong
The signaling pathway involving the R-spondins and its cognate receptor, GPR48/LGR4, is crucial in development and carcinogenesis. However, the functional implications of the R-spondin-GPR48/LGR4 pathway in thyroid remain to be identified. The aim of this study was to investigate the role of R-spondin-GPR48/LGR4 signaling in papillary thyroid carcinomas. We retrospectively reviewed a total of 214 patients who underwent total thyroidectomy and cervical lymph node dissection for papillary thyroid carcinoma. The role of GPR48/LGR4 in proliferation and migration was examined in thyroid cancer cell lines...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29345973/r-spondin-2-is-upregulated-in-idiopathic-pulmonary-fibrosis-and-affects-fibroblasts-behavior
#6
Adrián Munguía-Reyes, Yalbi I Balderas-Martínez, Carina Becerril, Marco Checa, Remedios Ramírez, Blanca Ortíz-Quintero, Jorge Meléndez-Zajgla, Annie Pardo, Moisés Selman
Idiopathic pulmonary fibrosis (IPF) is characterized by the expansion of the myofibroblasts population, excessive extracellular matrix accumulation, and destruction of the lung parenchyma. The R-spondins family (RSPO) comprises a group of proteins essential for development. From them, RSPO2 is expressed primarily in the lungs and its mutations cause severe defects in the respiratory tract. Interestingly, RSPO2 participates in the canonical WNT pathway, a critical route in the pathogenesis of IPF. Thus, the aim of this study was to examine the expression and putative role of RSPO2 in this disease...
January 18, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29339782/loss-of-disease-tolerance-during-citrobacter-rodentium-infection-is-associated-with-impaired-epithelial-differentiation-and-hyperactivation-of-t-cell-responses
#7
Eugene Kang, Guangyan Zhou, Mitra Yousefi, Romain Cayrol, Jianguo Xia, Samantha Gruenheid
Citrobacter rodentium is an intestinal mouse pathogen widely used as a model to study the mucosal response to infection. Inbred mouse strains suffer one of two fates following infection: self-limiting colitis or fatal diarrheal disease. We previously reported that Rspo2 is a major genetic determinant of the outcome of C. rodentium infection; Rspo2 induction during infection of susceptible mice leads to loss of intestinal function and mortality. Rspo2 induction does not impact bacterial colonization, but rather, impedes the ability of the host to tolerate C...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29181107/investigation-of-fusion-gene-expression-in-hct116-cells
#8
Yanmei Zhang, Juan Ren, Mengdie Fang, Xiaoju Wang
Colon cancer is the most common type of gastrointestinal cancer. A number of specific and sensitive biomarkers facilitate the diagnosis and monitoring of patients with colon cancer. Fusion genes are typically identified in cancer and a majority of the newly identified fusion genes are oncogenic in nature. Therefore, fusion genes are potential biomarkers and/or therapy targets in cancer. In the present study, the regulation of specific candidate fusion genes were investigated using Brother of the Regulator of Imprinted Sites (BORIS) in the HCT116 colon cancer cell line, which is a paralog of the fusion gene regulator CCCTC-binding factor (CTCF)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29168871/probing-impaired-neurogenesis-in-human-brain-organoids-exposed-to-alcohol
#9
Yujuan Zhu, Li Wang, Fangchao Yin, Yue Yu, Yaqing Wang, Matthew J Shepard, Zhengping Zhuang, Jianhua Qin
The fetal brain is highly vulnerable to ethanol exposure, which can trigger various long-term neuronal disabilities and cognitive dysfunctions. However, a comprehensive understanding of fetal brain development under ethanol exposure is challenging due to the limitations of animal models. Here, we propose a human induced pluripotent stem cell (hiPSC)-based 3D brain organoid model, and explore the mechanisms underlying neural dysfunctions in prenatal alcohol exposure (PAE) in vitro. Brain organoids were examined to resemble brain organogenesis in vivo at early stages during gestation, with specific features of neuronal differentiation, brain regionalization, and cortical organization...
December 11, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/29142306/an-exome-sequencing-based-approach-for-genome-wide-association-studies-in-the-dog
#10
Bart J G Broeckx, Thomas Derrien, Stéphanie Mottier, Valentin Wucher, Edouard Cadieu, Benoît Hédan, Céline Le Béguec, Nadine Botherel, Kerstin Lindblad-Toh, Jimmy H Saunders, Dieter Deforce, Catherine André, Luc Peelman, Christophe Hitte
Genome-wide association studies (GWAS) are widely used to identify loci associated with phenotypic traits in the domestic dog that has emerged as a model for Mendelian and complex traits. However, a disadvantage of GWAS is that it always requires subsequent fine-mapping or sequencing to pinpoint causal mutations. Here, we performed whole exome sequencing (WES) and canine high-density (cHD) SNP genotyping of 28 dogs from 3 breeds to compare the SNP and linkage disequilibrium characteristics together with the power and mapping precision of exome-guided GWAS (EG-GWAS) versus cHD-based GWAS...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127379/rspo3-antagonism-inhibits-growth-and-tumorigenicity-in-colorectal-tumors-harboring-common-wnt-pathway-mutations
#11
Marcus M Fischer, V Pete Yeung, Fiore Cattaruzza, Rajaa Hussein, Wan-Ching Yen, Christopher Murriel, James W Evans, Gilbert O'Young, Alayne L Brunner, Min Wang, Jennifer Cain, Belinda Cancilla, Ann Kapoun, Timothy Hoey
Activating mutations in the Wnt pathway are a characteristic feature of colorectal cancer (CRC). The R-spondin (RSPO) family is a group of secreted proteins that enhance Wnt signaling and RSPO2 and RSPO3 gene fusions have been reported in CRC. We have previously shown that Wnt pathway blockers exhibit potent combinatorial activity with taxanes to inhibit tumor growth. Here we show that RSPO3 antagonism synergizes with paclitaxel based chemotherapies in patient-derived xenograft models (PDX) with RSPO3 fusions and in tumors with common CRC mutations such as APC, β-catenin, or RNF43...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117559/an-eye-organoid-approach-identifies-six3-suppression-of-r-spondin-2-as-a-critical-step-in-mouse-neuroretina-differentiation
#12
Nozomu Takata, Deepti Abbey, Luciano Fiore, Sandra Acosta, Ruopeng Feng, Hyea Jin Gil, Alfonso Lavado, Xin Geng, Ashley Interiano, Geoffrey Neale, Mototsugu Eiraku, Yoshiki Sasai, Guillermo Oliver
Recent advances in self-organizing, 3-dimensional tissue cultures of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provided an in vitro model that recapitulates many aspects of the in vivo developmental steps. Using Rax-GFP-expressing ESCs, newly generated Six3-/- iPSCs, and conditional null Six3delta/f ;Rax-Cre ESCs, we identified Six3 repression of R-spondin 2 (Rspo2) as a required step during optic vesicle morphogenesis and neuroretina differentiation. We validated these results in vivo by showing that transient ectopic expression of Rspo2 in the anterior neural plate of transgenic mouse embryos was sufficient to inhibit neuroretina differentiation...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28743298/r-spondin2-a-novel-target-of-nobox-identification-of-variants-in-a-cohort-of-women-with-primary-ovarian-insufficiency
#13
Justine Bouilly, Isabelle Beau, Sara Barraud, Valérie Bernard, Brigitte Delemer, Jacques Young, Nadine Binart
BACKGROUND: R-spondin2 (Rspo2) is a secreted agonist of the canonical Wnt/β-catenin signaling pathway. Rspo2 plays a key role in development of limbs, lungs and hair follicles, and more recently during ovarian follicle development. Rspo2 heterozygous deficient female mice become infertile around 4 months of age mimicking primary ovarian insufficiency (POI). The study aimed to investigate the regulation of RSPO2 and its potential involvement in pathophysiology of POI. METHODS: We cloned the RSPO2 promoter and performed transcriptional assays to determine if RSPO2 can be regulated by NOBOX, an ovarian transcription factor...
July 25, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#14
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28695896/r-spondin-chromosome-rearrangements-drive-wnt-dependent-tumour-initiation-and-maintenance-in-the-intestine
#15
Teng Han, Emma M Schatoff, Charles Murphy, Maria Paz Zafra, John E Wilkinson, Olivier Elemento, Lukas E Dow
Defining the genetic drivers of cancer progression is a key in understanding disease biology and developing effective targeted therapies. Chromosome rearrangements are a common feature of human malignancies, but whether they represent bona fide cancer drivers and therapeutically actionable targets, requires functional testing. Here, we describe the generation of transgenic, inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer-associated EIF3E-RSPO2 and PTPRK-RSPO3 chromosome rearrangements in vivo...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28651234/microrna-493-suppresses-hepatocellular-carcinoma-tumorigenesis-through-down-regulation-of-anthrax-toxin-receptor-1-antxr1-and-r-spondin-2-rspo2
#16
Yuqiang Xu, Kuikui Ge, Junhao Lu, Jinjiang Huang, Wei Wei, Qingshan Huang
Hepatocellular carcinoma (HCC) is known as a highly prevalent cancer with a poor prognosis and short survival time, despite intensive research and clinical efforts. Increasing numbers of studies have reported that microRNAs are involved in the malignant behavior of hepatocellular carcinoma cells via directly targeting multiple oncogenes or tumor suppressors. Here, we report that the expression of microRNA-493 (miR-493) is decreased in HCC cell lines and in tumor tissues. Overexpression of miR-493 in HCC cells dramatically inhibited cell proliferation and colony-formation in vitro and inhibited tumor formation of HCC cell xenografts in vivo...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28600110/rspo2-suppresses-colorectal-cancer-metastasis-by-counteracting-the-wnt5a-fzd7-driven-noncanonical-wnt-pathway
#17
Xiaoming Dong, Wanqin Liao, Li Zhang, Xi Tu, Jin Hu, Tianke Chen, Xiaowei Dai, Yan Xiong, Weicheng Liang, Chaodong Ding, Rui Liu, Juji Dai, Ouchen Wang, Liting Lu, Xincheng Lu
R-spondins play critical roles in development, stem cell survival, and tumorigenicity by modulating Wnt/β-catenin signaling; however, the role of R-spondins in noncanonical Wnt signaling regulation remains largely unknown. We demonstrate here that R-spondin 2 (RSPO2) has an inhibitory effect on colorectal cancer (CRC) cell migration, invasion, and metastasis. Reduced RSPO2 expression was associated with tumor metastasis and poor survival in CRC patients. The metastasis-suppressive activity of RSPO2 was independent of the Wnt/β-catenin signaling pathway but dependent on the Fzd7-mediated noncanonical Wnt signaling pathway...
August 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28543708/comprehensive-characterization-of-rspo-fusions-in-colorectal-traditional-serrated-adenomas
#18
Shigeki Sekine, Reiko Ogawa, Taiki Hashimoto, Kojima Motohiro, Hiroshi Yoshida, Hirokazu Taniguchi, Yutaka Saito, Ohno Yasuhiro, Atsushi Ochiai, Nobuyoshi Hiraoka
AIMS: Traditional serrated adenoma (TSA) is a rare but distinct type of colorectal polyp. Our previous study showed that PTPRK-RSPO3 fusions are frequent and characteristic genetic alterations in TSAs. This study aimed to characterize comprehensively the prevalence and variability of RSPO fusions in colorectal TSAs. METHODS AND RESULTS: We examined RSPO expression and explored novel RSPO fusions in 129 TSAs, including 66 lesions analysed previously for WNT pathway gene mutations...
May 24, 2017: Histopathology
https://www.readbyqxmd.com/read/28472820/clinical-value-of-r-spondins-in-triple-negative-and-metaplastic-breast-cancers
#19
F Coussy, F Lallemand, S Vacher, A Schnitzler, W Chemlali, M Caly, A Nicolas, S Richon, D Meseure, R El Botty, L De-Plater, L Fuhrmann, T Dubois, S Roman-Roman, V Dangles-Marie, E Marangoni, I Bièche
BACKGROUND: RSPO ligands, activators of the Wnt/β-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC). METHODS: Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT-PCR. The effect of RSPO on the Wnt/β-catenin pathway activity was determined by luciferase assay, western blotting, and qRT-PCR. The effect of RSPO2 inhibition on proliferation was determined by using RSPO2 siRNAs...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28350845/abnormal-expression-of-mrna-microrna-alteration-and-aberrant-dna-methylation-patterns-in-rectal-adenocarcinoma
#20
Yang Hua, Xiukun Ma, Xianglong Liu, Xiangfei Yuan, Hai Qin, Xipeng Zhang
AIM: Rectal adenocarcinoma (READ) is a malignancy cancer with the high morbidity and motility worldwide. Our study aimed to explore the potential pathogenesis of READ through integrated analysis of gene expression profiling and DNA methylation data. METHODS: The miRNA, mRNA expression profiling and corresponding DNA methylation data were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs/ miRNAs/methylated regions (DEmRNA/DEmiRNAs) were identified in READ...
2017: PloS One
keyword
keyword
76422
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"