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https://www.readbyqxmd.com/read/28698137/ssecks-akap12-induces-repulsion-between-human-prostate-cancer-and-microvessel-endothelial-cells-through-the-activation-of-semaphorin-3f
#1
Wen Xie, Wei Su, Lijuan Zhang, Qingkun Shang, Bing Su
Metastasis remains the primary cause of prostate cancer related death. Cancer cells need to contact endothelial cells and disrupt endothelial junctions to cross the endothelium for invasion and metastasis. The suppression of heterotypic repulsion between cancer and endothelial cells allows cancer cells to invade into the surrounding tissue. Here, we demonstrate that SSeCKS/AKAP12 induced repulsion between human prostate cancer and microvessel endothelial cells, which was mediated by an angiogenesis inhibitor Semaphorin 3F...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28692932/axon-guidance-pathways-served-as-common-targets-for-human-speech-language-evolution-and-related-disorders
#2
Huimeng Lei, Zhangming Yan, Xiaohong Sun, Yue Zhang, Jianhong Wang, Caihong Ma, Qunyuan Xu, Rui Wang, Erich D Jarvis, Zhirong Sun
Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data...
July 7, 2017: Brain and Language
https://www.readbyqxmd.com/read/28689759/amplification-of-f-actin-disassembly-and-cellular-repulsion-by-growth-factor-signaling
#3
Jimok Yoon, Sang Bum Kim, Giasuddin Ahmed, Jerry W Shay, Jonathan R Terman
Extracellular cues that regulate cellular shape, motility, and navigation are generally classified as growth promoting (i.e., growth factors/chemoattractants and attractive guidance cues) or growth preventing (i.e., repellents and inhibitors). Yet, these designations are often based on complex assays and undefined signaling pathways and thus may misrepresent direct roles of specific cues. Here, we find that a recognized growth-promoting signaling pathway amplifies the F-actin disassembly and repulsive effects of a growth-preventing pathway...
July 3, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28683823/sema3a-drastically-suppresses-tumor-growth-in-oral-cancer-xenograft-model-of-mice
#4
Chao Huang, Yi Wang, Jian-Hua Huang, Weixian Liu
BACKGROUND: Multiple studies suggest anti-angiogenesis to be a promising and rational option in cancer treatment. Interestingly, the axonal sprouting inhibitor semaphorin 3A (Sema3A), a potent suppressor of tumor angiogenesis in various cancer models, is lowly expressed in human oral cancer. Thus, we hypothesized that overexpression of Sema3A in human oral cancer cells may have potential therapeutic effects. METHODS: The LentiSema3A-EGFP was first constructed and transduced to the tongue squamous cell carcinoma cell line SSC-9...
July 6, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28667171/neuropilin-1-promotes-hedgehog-signaling-through-a-novel-cytoplasmic-motif
#5
Justine M Pinskey, Nicole E Franks, Alexandra N McMellen, Roman J Giger, Benjamin L Allen
Hedgehog (HH) signaling critically regulates embryonic and postnatal development as well as adult tissue homeostasis, and its perturbation can lead to developmental disorders, birth defects, and cancers. Neuropilins (NRPs), which have well-defined roles in Semaphorin and VEGF signaling, positively regulate HH pathway function, although their mechanism of action in HH signaling remains unclear. Here, using luciferase-based reporter assays, we provide evidence that NRP1 regulates HH signaling, specifically at the level of GLI transcriptional activator function...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28659345/ablation-of-neuropilin-1-in-myeloid-cells-exacerbates-high-fat-diet-induced-insulin-resistance-through-nlrp3-inflammasome-in-vivo
#6
Xiaoyan Dai, Imoh Okon, Zhaoyu Liu, Tatiana Bedarida, Qilong Wang, Tharmarajan Ramprasath, Miao Zhang, Ping Song, Ming-Hui Zou
Neuropilin 1 (Nrp1), a co-receptor for class 3 semaphorins and growth factors, is highly expressed in vascular cells and myeloid cells including macrophages. Unlike well characterized pro-angiogeneic functions of endothelial cell Nrp1, the contributions of macrophage Nrp1 within the context of metabolic dysfunction remain to be established. The aim of this study was to determine the contributions of macrophage Nrp1 in high-fat diet (HFD; 60% kcal, 16 weeks)-instigated insulin resistance in vivo Insulin sensitivity and Nlrp3 inflammasome activation were monitored in HFD-fed wild-type (WT) and myeloid cell-specific Nrp1 knockout (Nrp1(myel-KO)) mice...
June 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28656278/semaphorin-4d-promotes-bone-invasion-in-head-and-neck-squamous-cell-carcinoma
#7
Hiroyuki Takada, Soichiro Ibaragi, Takanori Eguchi, Tatsuo Okui, Kyoichi Obata, Masanori Masui, Ayaka Morisawa, Kiyofumi Takabatake, Hotaka Kawai, Norie Yoshioka, Nur Mohammad Monsur Hassan, Tsuyoshi Shimo, Guo-Fu Hu, Hitoshi Nagatsuka, Akira Sasaki
Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression...
June 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28646017/ror%C3%AE-modulates-semaphorin-3e-transcription-and-neurovascular-interaction-in-pathological-retinal-angiogenesis
#8
Ye Sun, Chi-Hsiu Liu, Zhongxiao Wang, Steven S Meng, Samuel B Burnim, John Paul SanGiovanni, Theodore M Kamenecka, Laura A Solt, Jing Chen
Pathological proliferation of retinal blood vessels commonly causes vision impairment in proliferative retinopathies, including retinopathy of prematurity. Dysregulated crosstalk between the vasculature and retinal neurons is increasingly recognized as a major factor contributing to the pathogenesis of vascular diseases. Class 3 semaphorins (SEMA3s), a group of neuron-secreted axonal and vascular guidance factors, suppress pathological vascular growth in retinopathy. However, the upstream transcriptional regulators that mediate the function of SEMA3s in vascular growth are poorly understood...
June 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28643924/exosomes-novel-regulators-of-bone-remodelling-and-potential-therapeutic-agents-for-orthodontics
#9
REVIEW
L S Holliday, K P McHugh, J Zuo, J I Aguirre, J K Neubert, W J Rody
Recent studies suggest that exosomes are involved in intercellular communication required for the maintenance of healthy bone. Exosomes are small (30-150 nm in diameter) extracellular vesicles that are formed in multivesicular bodies and are released from cells as the multivesicular bodies fuse with the plasma membrane. Regulatory exosomes have the capacity to exert profound control over target cells. They can stimulate plasma membrane receptors and are also internalized by the target cell delivering proteins, lipids, small molecules and functional RNAs from the cell of origin...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28642891/safety-tolerability-of-the-anti-semaphorin-4d-antibody-vx15-2503-in-a-randomized-phase-1-trial
#10
Christopher LaGanke, Lawrence Samkoff, Keith Edwards, Lily Jung Henson, Pavle Repovic, Sharon Lynch, Lael Stone, David Mattson, Aaron Galluzzi, Terrence L Fisher, Christine Reilly, Laurie A Winter, John E Leonard, Maurice Zauderer
OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of VX15/2503 in a randomized, single-dose, dose-escalation, double-blind, placebo-controlled study enrolling adult patients with MS. METHODS: Single IV doses of VX15/2503 or placebo were administered. Ten patients each were randomized (4:1 randomization ratio) into 5 ascending dose cohorts of 1, 3, 6, 10, or 20 mg/kg. Safety, immunogenicity, PK/PD, MRI, ECG, and lymphocyte subset levels were evaluated...
July 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28637841/protein-tyrosine-phosphatase-%C3%AE-mediates-the-sema3a-induced-cortical-basal-dendritic-arborization-through-the-activation-of-fyn-tyrosine-kinase
#11
Fumio Nakamura, Takako Okada, Maria Shishikura, Noriko Uetani, Masahiko Taniguchi, Takeshi Yagi, Yoichiro Iwakura, Toshio Ohshima, Yoshio Goshima, Stephen M Strittmatter
Leukocyte common antigen related (LAR) class protein tyrosine phosphatases (PTPs) are critical for axonal guidance; however, their relation to specific guidance cues is poorly defined. We here show that PTP-3, LAR homologue in C. elegans, is involved in axon guidance regulated by Sema2A-signaling. PTPδ, one of vertebrate LAR class PTPs, participates in Sema3A-induced growth cone collapse response of primary cultured dorsal root ganglion neurons from M. musculus embryos. In vivo, however, the contribution of PTPδ in Sema3A-regualted axon guidance was minimal...
June 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28636974/sema3a-partially-reverses-vegf-effects-through-binding-to-neuropilin-1
#12
Bruna Palodetto, Adriana da Silva Santos Duarte, Matheus Rodrigues Lopes, Flavia Adolfo Corrocher, Fernanda Marconi Roversi, Fernanda Soares Niemann, Karla Priscila Vieira Ferro, Ana Leda Figueiredo Longhini, Paula Melo Campos, Patricia Favaro, Sara Teresinha Olalla Saad
Cross-talk between hematopoietic stem cells (HSCs) and bone marrow stromal cells (BMSCs) is essential for HSCs regulation and leukemogenesis. Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, we found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34(+) HSCs and semaphorin 3A (SEMA3A) in BMSCs. To better understand the role of VEGFA and SEMA3A in leukemogenesis, we recruited 30 myelodysplastic syndrome (MDS) patients, 29 acute myeloid leukemia (6 secondary to MDS) patients and 12 controls...
June 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28635959/optogenetic-activation-of-plexin-b1-reveals-contact-repulsion-between-osteoclasts-and-osteoblasts
#13
Abhijit Deb Roy, Taofei Yin, Shilpa Choudhary, Vladimir Rodionov, Carol C Pilbeam, Yi I Wu
During bone remodelling, osteoclasts induce chemotaxis of osteoblasts and yet maintain spatial segregation. We show that osteoclasts express the repulsive guidance factor Semaphorin 4D and induce contact inhibition of locomotion (CIL) in osteoblasts through its receptor Plexin-B1. To examine causality and elucidate how localized Plexin-B1 stimulation may spatiotemporally coordinate its downstream targets in guiding cell migration, we develop an optogenetic tool for Plexin-B1 designated optoPlexin. Precise optoPlexin activation at the leading edge of migrating osteoblasts readily induces local retraction and, unexpectedly, distal protrusions to steer cells away...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28634005/semaphorin-3e-alleviates-hallmarks-of-house-dust-mite-induced-allergic-airway-disease
#14
Hesam Movassagh, Lianyu Shan, Jonathan S Duke-Cohan, Andrew J Halayko, Jude E Uzonna, Abdelilah S Gounni
Semaphorins are an essential family of guidance cues ubiquitously expressed in various organs, which play diverse developmental, homeostatic, and pathological roles. Semaphorin 3E (Sema3E), initially identified as a neuronal chemorepellent, is involved in the regulation of cell migration, proliferation, and angiogenesis. However, expression and function of Sema3E in allergic asthma has not been extensively investigated. We determined the expression of Sema3E in the airways and its effect on airway inflammation, hyperresponsiveness, and remodeling as pathological features of allergic asthma provoked by house dust mite in vivo...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28632130/the-laminar-organization-of-the-drosophila-ellipsoid-body-is-semaphorin-dependent-and-prevents-the-formation-of-ectopic-synaptic-connections
#15
Xiaojun Xie, Masashi Tabuchi, Matthew P Brown, Sarah P Mitchell, Mark N Wu, Alex L Kolodkin
The ellipsoid body (EB) in the Drosophila brain is a central complex (CX) substructure that harbors circumferentially laminated ring (R) neuron axons and mediates multifaceted sensory integration and motor coordination functions. However, what regulates R axon lamination and how lamination affects R neuron function remain unknown. We show here that the EB is sequentially innervated by small-field and large-field neurons and that early developing EB neurons play an important regulatory role in EB laminae formation...
June 20, 2017: ELife
https://www.readbyqxmd.com/read/28626864/detecting-genetic-association-through-shortest-paths-in-a-bidirected-graph
#16
Masao Ueki, Yoshinori Kawasaki, Gen Tamiya
Genome-wide association studies (GWASs) commonly use marginal association tests for each single-nucleotide polymorphism (SNP). Because these tests treat SNPs as independent, their power will be suboptimal for detecting SNPs hidden by linkage disequilibrium (LD). One way to improve power is to use a multiple regression model. However, the large number of SNPs preclude simultaneous fitting with multiple regression, and subset regression is infeasible because of an exorbitant number of candidate subsets. We therefore propose a new method for detecting hidden SNPs having significant yet weak marginal association in a multiple regression model...
June 19, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28624895/semaphorin4d-plexinb1-signaling-attenuates-photoreceptor-outer-segment-phagocytosis-by-reducing-rac1-activity-of-rpe-cells
#17
Ayelen Bulloj, Arvydas Maminishkis, Masayuki Mizui, Silvia C Finnemann
Semaphorins form a family of secreted and membrane-bound molecules that were identified originally as axonal guidance factors during neuronal development. Given their wide distribution in many including mature tissues, semaphorin 4D (sema4D) and its main functional receptor plexin B1 (plxnB1) are expected to fulfill additional functions that remain to be uncovered. A main characteristic of the plexin receptor family is its ability to reorganize the cytoskeleton. PlxnB1 specifically may directly interact with Rho family GTPases to regulate F-actin driven pathways in cells in culture...
June 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28610953/a-thirty-year-quest-for-a-role-of-r-ras-in-cancer-from-an-oncogene-to-a-multitasking-gtpase
#18
Wai Nam Liu, Mingfei Yan, Andrew M Chan
Since the identification of R-Ras, which is the first Ras-related GTPase isolated based on sequence similarity to the classical RAS oncogene, more than 160 members of the Ras superfamily of GTPases have been identified and classified into the Ras, Rho, Rap, Rab, Ran, Arf, Rheb, RGK, Rad, Rit, and Miro subfamilies. R-Ras belongs to the Ras subfamily of small G-proteins, which are frequently implicated in cell growth and differentiation. Although the roles of R-Ras in cellular transformation and integrin-mediated cell adhesion have been extensively studied, the physiological function of this enigmatic G-protein was only revealed when a mouse strain deficient in R-Ras was generated...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28602571/cytoplasmic-neuropilin-2-is-associated-with-metastasis-and-a-poor-prognosis-in-early-tongue-cancer-patients
#19
H S Ong, S Gokavarapu, Q Xu, Z Tian, J Li, T Ji, C P Zhang
Neuropilin 2 (Nrp2) plays an important role in regulating lymphangiogenesis. Nrp2 expression in early tongue cancer was investigated to predict lymph node metastasis and the long-term prognosis. The relationships between clinicopathological variables of cT1-T2N0 tongue squamous cell carcinoma (SCC) and overexpression of Nrp2, vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 3 (VEGFR3), and semaphorin 3F (Sema3F) were analyzed. Expression levels were compared using oral SCC cell lines...
June 8, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28581515/gata3-targets-semaphorin-3b-in-mammary-epithelial-cells-to-suppress-breast-cancer-progression-and-metastasis
#20
P Shahi, C-Y Wang, J Chou, C Hagerling, H Gonzalez Veloso, A Ruderisch, Y Yu, M-D Lai, Z Werb
Semaphorin 3B (SEMA3B) is a secreted axonal guidance molecule that is expressed during development and throughout adulthood. Recently, SEMA3B has emerged as a tumor suppressor in non-neuronal cells. Here, we show that SEMA3B is a direct target of GATA3 transcriptional activity. GATA3 is a key transcription factor that regulates genes involved in mammary luminal cell differentiation and tumor suppression. We show that GATA3 relies on SEMA3B for suppression of tumor growth. Loss of SEMA3B renders GATA3 inactive and promotes aggressive breast cancer development...
June 5, 2017: Oncogene
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