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https://www.readbyqxmd.com/read/28732387/the-micrornas-mir-200b-3p-and-mir-429-5p-target-the-limk1-cfl1-pathway-to-inhibit-growth-and-motility-of-breast-cancer-cells
#1
Dengfeng Li, Hong Wang, Hongming Song, Hui Xu, Bingkun Zhao, Chenyang Wu, Jiashu Hu, Tianqi Wu, Dan Xie, Junyong Zhao, Qiang Shen, Lin Fang
Triple-negative breast cancer (TNBC) has the worst prognosis of all subtypes of breast cancer (BC), with limited options for conventional therapy and no targeted therapies. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. In this study, we aimed to determine whether two members of the miR-200 family, miR-200b-3p and miR-429-5p, are involved in BC cell proliferation and motility and to elucidate their target genes and pathways. We performed a meta-analysis that reveals down-regulated expression of miR-200b-3p and miR-429-5p in BC tissues and cell lines, consistent with a lower expression of miR-200b-3p and miR-429-5p in MDA-MB-231 and HCC1937 cells than in MCF-7 and MCF-10 cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708581/cofilin-1-and-phosphoglycerate-kinase-1-as-promising-indicators-for-glioma-radiosensibility-and-prognosis
#2
Wenbo Sun, Hua Yan, Chunfa Qian, Chenhan Wang, Mengjie Zhao, Yuchi Liu, Yujie Zhong, Hongyi Liu, Hong Xiao
Glioma is a primary malignancy in central nervous system. Radiotherapy has been used as one of the standard treatments for glioma for decades. Since radioresistance can reduce the curative efficacy of radiotherapy in glioma, investigating the cause of radioresistance and predicting the tumour radiosensibility appeared particularly important. We previously reported that CFL1 and PGK1 are over-expressed in radioresistant U251 glioma cells. In this study, the level of CFL1 and PGK1 of 113 glioma tissues were measured by ELISA method...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704726/bnip3-induction-by-hypoxia-stimulates-fasn-dependent-free-fatty-acid-production-enhancing-therapeutic-potential-of-umbilical-cord-blood-derived-human-mesenchymal-stem-cells
#3
Hyun Jik Lee, Young Hyun Jung, Gee Euhn Choi, So Hee Ko, Sei-Jung Lee, Sang Hun Lee, Ho Jae Han
Mitophagy under hypoxia is an important factor for maintaining and regulating stem cell functions. We previously demonstrated that fatty acid synthase (FASN) induced by hypoxia is a critical lipid metabolic factor determining the therapeutic efficacy of umbilical cord blood-derived human mesenchymal stem cells (UCB-hMSCs). Therefore, we investigated the mechanism of a major mitophagy regulator controlling lipid metabolism and therapeutic potential of UCB-hMSCs. This study revealed that Bcl2/adenovirus E1B 19kDa protein-interacting protein 3 (BNIP3)-dependent mitophagy is important for reducing mitochondrial reactive oxygen species accumulation, anti-apoptosis, and migration under hypoxia...
July 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28696540/conserved-hydrophobic-residues-in-the-carp-%C3%AE-sheet-domain-of-cyclase-associated-protein-are-involved-in-actin-monomer-regulation
#4
Shohei Iwase, Shoichiro Ono
Cyclase-associated protein (CAP) is a multi-domain protein that promotes actin filament dynamics. The C-terminal region of CAP contains a CAP and X-linked retinitis pigmentosa 2 protein (CARP) domain (or a β-sheet domain), which binds to actin monomer and is essential for enhancing exchange of actin-bound nucleotides. However, how the CARP domain binds to actin is not clearly understood. Here, we report that conserved hydrophobic residues in the CARP domain play important roles in the function of CAP to regulate actin dynamics...
July 11, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28692057/the-interactome-of-metabolic-enzyme-carbonic-anhydrase-ix-reveals-novel-roles-in-tumor-cell-migration-and-invadopodia-mmp14-mediated-invasion
#5
M Swayampakula, P C McDonald, M Vallejo, E Coyaud, S C Chafe, A Westerback, G Venkateswaran, J Shankar, G Gao, E M N Laurent, Y Lou, K L Bennewith, C T Supuran, I R Nabi, B Raught, S Dedhar
Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX 'interactome' in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins with potential roles in tumor progression. High confidence proteins identified include metabolic transporters, β1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14 (MMP14)...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28679472/nkcc1-regulates-migration-ability-of-glioblastoma-cells-by-modulation-of-actin-dynamics-and-interacting-with-cofilin
#6
Paula Schiapparelli, Hugo Guerrero-Cazares, Roxana Magaña-Maldonado, Susan M Hamilla, Sara Ganaha, Eric Goulin Lippi Fernandes, Chuan-Hsiang Huang, Helim Aranda-Espinoza, Peter Devreotes, Alfredo Quinones-Hinojosa
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD)...
June 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28670365/lc-0882-targets-pak4-and-inhibits-pak4-related-signaling-pathways-to-suppress-the-proliferation-and-invasion-of-gastric-cancer-cells
#7
Hong-Yan Zhang, Jian Zhang, Chen-Zhou Hao, Ying Zhou, Jian Wang, Mao-Sheng Cheng, Dong-Mei Zhao, Feng Li
Gastric cancer is the most common malignant tumor and globally the third leading cause of cancer-related deaths. Therefore, there exists an urgent need to identify new effective gastric cancer treatments. Given the important roles in tumorigenesis and progression, p21-activated kinase 4 (PAK4) has been regarded as an attractive high-value druggable target. In this study, we examined the effects and molecular mechanisms of action of the small molecular compound LC-0882 on gastric cancer cells in vitro. LC-0882 was found to significantly inhibit the proliferation of human gastric cancer cells by repressing phospho-PAK4/cyclin D1 and CDK4/6 expression...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28668486/glycogenolysis-an-astrocyte-specific-reaction-is-essential-for-both-astrocytic-and-neuronal-activities-involved-in-learning
#8
REVIEW
Leif Hertz, Ye Chen
In brain glycogen, formed from glucose, is degraded (glycogenolysis) in astrocytes but not in neurons. Although most of the degradation follows the same pathway as glucose, its breakdown product, l-lactate, is released from astrocytes in larger amounts than glucose when glycogenolysis is activated by noradrenaline. However, this is not the case when glycogenolysis is activated by high potassium ion (K(+)) concentrations - possibly because noradrenaline in contrast to high K(+) stimulates glycogenolysis by an increase not only in free cytosolic Ca(2+) concentration ([Ca(2+)]i) but also in cyclic AMP (c-AMP), which may increase the expression of the monocarboxylate transporter through which it is released...
June 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28661046/activation-of-camkk%C3%AE-ampk%C3%AE-pathway-by-2-ag-in-human-platelets
#9
Maria Grazia Signorello, Giuliana Leoncini
The objective of this study was to determine whether AMPK is activated by 2-arachidonoylglycerol (2-AG) and participates to the cytoskeleton control in human platelets. We found that 2-AG stimulates the AMPKα activation through a Ca(2+) /Calmodulin-dependent pathway as the specific inhibition of the CaMKKβ by STO-609 inhibits the AMPKα phosphorylation/activation. Moreover the CaMKKβ/AMPKα pathway activated by 2-AG is involved in the phosphorylation of cofilin, vasodilator stimulated phosphoprotein (VASP) and myosin light chain (MLCs)...
June 29, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28660097/fasudil-a-clinically-used-rock-inhibitor-stabilizes-rod-photoreceptor-synapses-after-retinal-detachment
#10
Ellen Townes-Anderson, Jianfeng Wang, Éva Halász, Ilene Sugino, Amy Pitler, Ian Whitehead, Marco Zarbin
PURPOSE: Retinal detachment disrupts the rod-bipolar synapse in the outer plexiform layer by retraction of rod axons. We showed that breakage is due to RhoA activation whereas inhibition of Rho kinase (ROCK), using Y27632, reduces synaptic damage. We test whether the ROCK inhibitor fasudil, used for other clinical applications, can prevent synaptic injury after detachment. METHODS: Detachments were made in pigs by subretinal injection of balanced salt solution (BSS) or fasudil (1, 10 mM)...
June 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28647699/proteomic-analysis-of-normal-and-cancer-cervical-cell-lines-reveals-deregulation-of-cytoskeleton-associated-proteins
#11
Kalliopi I Pappa, Vasiliki Lygirou, Georgia Kontostathi, Jerome Zoidakis, Manousos Makridakis, Konstantinos Vougas, George Daskalakis, Alexander Polyzos, Nicholas P Anagnou
BACKGROUND: Both HPV-positive and -negative cervical cancers are primarily associated with features of cell cycle and cytoskeletal disruption; however, the actual biological processes affected remain elusive. To this end, we systematically characterized the intracellular proteomic profiles of four distinct and informative cervical cell lines. MATERIALS AND METHODS: Cell extracts from a normal cervical (HCK1T) and three cervical cancer cell lines, one HPV-negative (C33A), and two HPV-positive, SiHa (HPV16+) and HeLa (HPV18+), were analyzed by 2-dimensional electrophoresis and differentially expressed proteins were identified by MALDI-TOF mass spectrometry, while differential expression was confirmed by western blot analysis...
July 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28639351/titanium-released-from-dental-implant-enhances-pre-osteoblast-adhesion-by-ros-modulating-crucial-intracellular-pathways
#12
M C Rossi, Fjb Bezerra, R A Silva, B P Crulhas, Cjc Fernandes, A S Nascimento, V A Pedrosa, P Padilha, W F Zambuzzi
It is important to understand the cellular and molecular events that occur at the cell-material interface of implants used for bone repair. The mechanisms involved in the initial stages of osteoblast interactions with the surface of the implant material must be decisive for cell fating surrounding them. In order to address this issue, we decided to investigate if conditioned medium for dental implants was able to modulate murine pre-osteoblast metabolism. First, we determined the concentration of titanium (Ti)-containing conditioned medium and found that it was 2-fold increased (p<0...
June 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28636918/actin-filament-strain-promotes-severing-and-cofilin-dissociation
#13
Anthony C Schramm, Glen M Hocky, Gregory A Voth, Laurent Blanchoin, Jean-Louis Martiel, Enrique M De La Cruz
Computational and structural studies have been indispensable in investigating the molecular origins of actin filament mechanical properties and modulation by the regulatory severing protein cofilin. All-atom molecular dynamics simulations of cofilactin filament structures determined by electron cryomicroscopy reveal how cofilin enhances the bending and twisting compliance of actin filaments. Continuum mechanics models suggest that buckled cofilactin filaments localize elastic energy at boundaries between bare and cofilin-decorated segments because of their nonuniform elasticity, thereby accelerating filament severing...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28627240/quercetin-has-antimetastatic-effects-on-gastric-cancer-cells-via-the-interruption-of-upa-upar-function-by-modulating-nf-%C3%AE%C2%BAb-pkc-%C3%AE-erk1-2-and-ampk%C3%AE
#14
Hai Li, Chen Chen
Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28625781/adf-cofilin-accelerates-actin-dynamics-by-severing-filaments-and-promoting-their-depolymerization-at-both-ends
#15
Hugo Wioland, Berengere Guichard, Yosuke Senju, Sarah Myram, Pekka Lappalainen, Antoine Jégou, Guillaume Romet-Lemonne
Actin-depolymerizing factor (ADF)/cofilins contribute to cytoskeletal dynamics by promoting rapid actin filament disassembly. In the classical view, ADF/cofilin sever filaments, and capping proteins block filament barbed ends whereas pointed ends depolymerize, at a rate that is still debated. Here, by monitoring the activity of the three mammalian ADF/cofilin isoforms on individual skeletal muscle and cytoplasmic actin filaments, we directly quantify the reactions underpinning filament severing and depolymerization from both ends...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28625780/enhanced-depolymerization-of-actin-filaments-by-adf-cofilin-and-monomer-funneling-by-capping-protein-cooperate-to-accelerate-barbed-end-growth
#16
Shashank Shekhar, Marie-France Carlier
A living cell's ability to assemble actin filaments in intracellular motile processes is directly dependent on the availability of polymerizable actin monomers, which feed polarized filament growth [1, 2]. Continued generation of the monomer pool by filament disassembly is therefore crucial. Disassemblers like actin depolymerizing factor (ADF)/cofilin and filament cappers like capping protein (CP) are essential agonists of motility [3-8], but the exact molecular mechanisms by which they accelerate actin polymerization at the leading edge and filament turnover has been debated for over two decades [9-12]...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28608282/poly-adp-ribosylated-proteins-in-mononuclear-cells-from-patients-with-type-2-diabetes-identified-by-proteomic-studies
#17
Alessandra Giorgi, Italo Tempera, Giorgia Napoletani, Diego Drovandi, Cinzia Potestà, Sara Martire, Elisabetta Mandosi, Tiziana Filardi, M Eugenia Schininà, Susanna Morano, Maria d'Erme, Bruno Maras
AIMS: In diabetes, hyperglycemia increases reactive oxygen species that induce DNA damage and poly(ADP-ribose)polymerase activation. The aim of this study is to characterize the proteomic profile and the role of poly(ADP-ribosylation) in patients with type 2 diabetes. METHODS: A proteomic platform based on 2DE and MALDI-ToF spectrometry was applied to peripheral blood mononuclear cells obtained from two different cohorts in which diabetic (n = 14) and normoglycemic patients (n = 11) were enrolled...
June 12, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28599494/cucurbitacin-e-induces-apoptosis-of-human-prostate-cancer-cells-via-cofilin-1-and-mtorc1
#18
Xiaolong He, Qi Gao, Yayong Qiang, Wei Guo, Yadong Ma
Cucurbitacin E is an important member of the cucurbitacin family and exhibits inhibitory effects in various types of cancer. Cucurbitacin is a potential antineoplastic drug; however, its anticancer effect in human prostate cancer (PC) remains unknown. The aim of the present study was to determine whether the effect of cucurbitacin E on the cell viability and apoptosis of the human PC cell line, LNCaP, was mediated by cofilin-1- and mammalian target of rapamycin (mTOR). The results of the present study demonstrated that cucurbitacin E significantly exhibited cytotoxicity, suppressed cell viability (P<0...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598765/shigella-depends-on-sepa-to-destabilize-the-intestinal-epithelial-integrity-via-cofilin-activation
#19
Ana Maldonado-Contreras, James R Birtley, Erik Boll, Yun Zhao, Karen L Mumy, Juan Toscano, Seyoum Ayehunie, Hans-Christian Reinecker, Lawrence J Stern, Beth A McCormick
Shigella is unique among enteric pathogens, as it invades colonic epithelia through the basolateral pole. Therefore, it has evolved the ability to breach the intestinal epithelial barrier to deploy an arsenal of effector proteins, which permits bacterial invasion and leads to a severe inflammatory response. However, the mechanisms used by Shigella to regulate epithelial barrier permeability remain unknown. To address this question, we used both an intestinal polarized model and a human ex-vivo model to further characterize the early events of host-bacteria interactions...
June 9, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28588454/reelin-signaling-inactivates-cofilin-to-stabilize-the-cytoskeleton-of-migrating-cortical-neurons
#20
REVIEW
Michael Frotscher, Shanting Zhao, Shaobo Wang, Xuejun Chai
Neurons are highly polarized cells. They give rise to several dendrites but only one axon. In addition, many neurons show a preferred orientation. For example, pyramidal neurons of the cerebral cortex extend their apical dendrites toward the cortical surface while their axons run in opposite direction toward the white matter. This characteristic orientation reflects the migratory trajectory of a pyramidal cell during cortical development: the leading process (the future apical dendrite) extends toward the marginal zone (MZ) and the trailing process (the future axon) toward the intermediate zone (IZ) while the cells migrate radially to reach their destination in the cortical plate (CP)...
2017: Frontiers in Cellular Neuroscience
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