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Migration and lysosome

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https://www.readbyqxmd.com/read/29331585/cathepsin-l-promotes-ionizing-radiation-induced-u251-glioma-cell-migration-and-invasion-through-regulating-the-gsk-3%C3%AE-cux1-pathway
#1
Yao Fei, Yajie Xiong, Xiao Shen, Yifan Zhao, Ying Zhu, Long Wang, Zhongqin Liang
Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by tumor cells. Our previous study found that CTSL was involved in ionizing radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase of glioma invasion and migration. However, the mechanisms by which CTSL promoted this IR-induced glioma migration and invasion remained unclear. In this study, we demonstrated that IR reduced glycogen synthase kinase-3β (GSK-3β) activity, via the CTSL-mediated phosphorylation of its serine-9 residue, in U251 cells...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29318884/inhibition-of-epithelial-mesenchymal-transition-and-tissue-regeneration-by-waterborne-titanium-dioxide-nanoparticles
#2
Xiaojiao Li, Lele Song, Xingjie Hu, Chang Liu, Jiye Shi, Hui Wang, Lixing Zhan, Haiyun Song
Titanium dioxide nanoparticles (TiO2NPs) are among the most widely manufactured nanomaterials with broad applications in food industry, cosmetics and medicine. Whereas the toxicity of TiO2NPs at high doses has been extensively explored, potential health risks of TiO2NPs exposure at non-toxic concentrations remain poorly understood. Epithelial-mesenchymal transition (EMT) plays pivotal roles in a diversity of physiological and pathological processes including tissue regeneration and cancer metastasis. In this study, we find that cellular uptake of TiO2NPs inhibits EMT-mediated cell remodeling and cell migration without exhibiting cytotoxicity...
January 10, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29317261/insulin-induced-translocation-of-ir-to-the-nucleus-in-insulin-responsive-cells-requires-a-nuclear-translocation-sequence
#3
Dov Kesten, Miriam Horovitz-Fried, Tamar Brutman-Barazani, Sanford R Sampson
Insulin binding to its cell surface receptor (IR) activates a cascade of events leading to its biological effects. The Insulin-IR complex is rapidly internalized and then is either recycled back to the plasma membrane or sent to lysosomes for degradation. Although most of the receptor is is recycled or degraded, a small amount may escape this pathway and migrate to the nucleus of the cell where it might be important in promulgation of receptor signals. In this study we explored the mechanism by which insulin induces IR translocation to the cell nucleus...
January 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29316035/transcription-factor-eb-tfeb-influences-invasion-and-migration-in-oral-squamous-cell-carcinomas
#4
Hiroshi Sakamoto, Kentaro Yamashita, Kuniaki Okamoto, Tomoko Kadowaki, Eiko Sakai, Masahiro Umeda, Takayuki Tsukuba
OBJECTIVE: Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and plays an important role in various cancers. However, the function of TFEB in oral squamous cell carcinomas has not been examined. The aim of this study was to elucidate the role of TFEB in oral squamous cell carcinomas. MATERIALS AND METHODS: Expression levels of TFEB were examined in six different human oral squamous carcinoma cells: HSC2, HSC3, HSC4, SAS, OSC20, and SCC25...
January 9, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29313411/inhibition-of-wnt-ctnnb1-signaling-upregulates-sqstm1-and-sensitizes-glioblastoma-cells-to-autophagy-blockers
#5
Mireia Nager, Marta Crespí Sallán, Anna Visa, Charumathi Pushparaj, Maria Santacana, Anna Macià, Andrée Yeramian, Carles Cantí, Judit Herreros
WNT-CTNN1B signaling promotes cancer cell proliferation and stemness. Furthermore, recent evidence indicates that macroautophagy/autophagy regulates WNT signaling. Here we investigated the impact of inhibiting WNT signaling on autophagy in glioblastoma (GBM), a devastating brain tumor. Inhibiting TCF, or silencing TCF4 or CTNNB1/β-catenin upregulated SQSTM1/p62 in GBM at transcriptional and protein levels and, in turn, autophagy. DKK1/Dickkopf1, a canonical WNT receptor antagonist, also induced autophagic flux...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29311744/mutations-in-vps15-perturb-neuronal-migration-in-mice-and-are-associated-with-neurodevelopmental-disease-in-humans
#6
Thomas Gstrein, Andrew Edwards, Anna Přistoupilová, Ines Leca, Martin Breuss, Sandra Pilat-Carotta, Andi H Hansen, Ratna Tripathy, Anna K Traunbauer, Tobias Hochstoeger, Gavril Rosoklija, Marco Repic, Lukas Landler, Viktor Stránecký, Gerhard Dürnberger, Thomas M Keane, Johannes Zuber, David J Adams, Jonathan Flint, Tomas Honzik, Marta Gut, Sergi Beltran, Karl Mechtler, Elliott Sherr, Stanislav Kmoch, Ivo Gut, David A Keays
The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling...
January 8, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29303993/endolysosomal-cation-channels-and-cancer-a-link-with-great-potential
#7
REVIEW
Christian Grimm, Karin Bartel, Angelika M Vollmar, Martin Biel
The endolysosomal system (ES) consists of lysosomes; early, late, and recycling endosomes; and autophagosomes. It is a key regulator not only of macromolecule degradation and recycling, plasma membrane repair, homeostasis, and lipid storage, but also of antigen presentation, immune defense, cell motility, cell death signaling, tumor growth, and cancer progression. In addition, it plays a critical role in autophagy, and the autophagy-lysosome pathway is intimately associated with the hallmarks of cancer, such as escaping cell death pathways, evading immune surveillance, and deregulating metabolism...
January 5, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29285208/rab-coupling-protein-mediated-endosomal-recycling-of-n-cadherin-influences-cell-motility
#8
Andrew J Lindsay, Mary W McCaffrey
Rab coupling protein (RCP) is a Rab GTPase effector that functions in endosomal recycling. The RCP gene is frequently amplified in breast cancer, leading to increased cancer aggressiveness. Furthermore, RCP enhances the motility of ovarian cancer cells by coordinating the recycling of α5β1 integrin and EGF receptor to the leading edge of migrating cells. Here we report that RCP also influences the motility of lung adenocarcinoma cells. Knockdown of RCP inhibits the motility of A549 cells in 2D and 3D migration assays, while its overexpression enhances migration in these assays...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284682/glucocorticoids-induce-differentiation-of-monocytes-towards-macrophages-that-share-functional-and-phenotypical-aspects-with-erythroblastic-island-macrophages
#9
Esther Heideveld, Lea A Hampton-O'Neil, Stephen J Cross, Floris P J van Alphen, Maartje van den Biggelaar, Ashley M Toye, Emile van den Akker
The classical central macrophage found in erythroblastic islands plays an important role in erythroblast differentiation, proliferation and enucleation in the bone marrow. Convenient human in vitro models to facilitate the study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance in vitro erythropoiesis by supporting hematopoietic stem cell survival. Here, we describe that these specific macrophages also support erythropoiesis. Human monocytes cultured in serum-free media supplemented with stem cell factor, erythropoietin, lipids and dexamethasone differentiate towards macrophages expressing CD16, CD163, CD169, CD206, CXCR4 and the phagocytic TAM-receptor family...
December 28, 2017: Haematologica
https://www.readbyqxmd.com/read/29282290/phosphoinositide-conversion-in-endocytosis-and-the-endolysosomal-system
#10
Alexander Wallroth, Volker Haucke
Phosphoinositides (PIs)1 are phospholipids that perform crucial cell functions ranging from cell migration and signaling to membrane trafficking, by serving as signposts of compartmental membrane identity. Although phosphatidylinositol 4,5-bisphosphate, 3-phosphate, and 3,5-bisphosphate are commonly considered as hallmarks of the plasma membrane, endosomes, and lysosomes, these compartments contain other functionally important PIs. Here, we review the roles of PIs in different compartments of the endolysosomal system in mammalian cells and discuss the mechanisms that spatiotemporally control PI conversion in endocytosis and endolysosomal membrane dynamics during endosome maturation and sorting...
December 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29246726/k-ras-mutation-promotes-ionizing-radiation-induced-invasion-and-migration-of-lung-cancer-in-part-via-the-cathepsin-l-cux1-pathway
#11
Long Wang, Yifan Zhao, Yajie Xiong, Wenjuan Wang, Yao Fei, Caihong Tan, Zhongqin Liang
K-ras mutation is involved in cancer progression including invasion and migration, but the underlying mechanism is not yet clear. Cathepsin L is a lysosomal cysteine protease and has recently been associated with invasion and migration in human cancers when it is overexpressed. Our recent studies have shown that ionizing radiation (IR) enhanced expression of cathepsin L and increased invasion and migration of tumor cells, but the molecular mechanism is still unclear. In the present study, the effects of K-ras mutation and IR induced invasion and migration of lung cancer as well as the underlying mechanisms were investigated both in vitro and in vivo...
December 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29187366/cell-confluence-regulates-claudin-2-expression-possible-role-for-zo-1-and-rac
#12
Yasaman Amoozadeh, Shaista Anwer, Qinghong Dan, Shruthi Venugopal, Yixuan Shi, Emily Branchard, Elisabeth Liedtke, Menachem Ailenberg, Ori D Rotstein, Andras Kapus, Katalin Szaszi
Claudin-2 (Cldn-2) is a channel-forming tight junction (TJ) protein in the proximal tubules that mediates paracellular Na+ transport and has also emerged as a regulator of proliferation and migration. Expression of Cldn-2 is altered by numerous stimuli, but the underlying mechanisms remain incompletely understood. Here we show that Cldn-2 protein and mRNA expression were low in sub-confluent tubular cells and increased during junction maturation. Cldn-1 or occludin did not exhibit similar confluence-dependence...
November 29, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29183341/kinetics-and-dissolution-of-intratracheally-administered-nickel-oxide-nanomaterials-in-rats
#13
Naohide Shinohara, Guihua Zhang, Yutaka Oshima, Toshio Kobayashi, Nobuya Imatanaka, Makoto Nakai, Takeshi Sasaki, Kenji Kawaguchi, Masashi Gamo
BACKGROUND: The toxicokinetics of nanomaterials are an important factor in toxicity, which may be affected by slow clearance and/or distribution in the body. METHODS: Four types of nickel oxide (NiO) nanoparticles were single-administered intratracheally to male F344 rats at three doses of 0.67-6.0 mg/kg body weight. The rats were sacrificed under anesthesia and the lung, thoracic lymph nodes, bronchoalveolar lavage fluid, liver, and other organs were sampled for Ni burden measurement 3, 28, and 91 days post-administration; Ni excretion was measured 6 and 24 h after administration...
November 28, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29176619/stim1-promotes-migration-phagosomal-maturation-and-antigen-cross-presentation-in-dendritic-cells
#14
Paula Nunes-Hasler, Sophia Maschalidi, Carla Lippens, Cyril Castelbou, Samuel Bouvet, Daniele Guido, Flavien Bermont, Esen Y Bassoy, Nicolas Page, Doron Merkler, Stéphanie Hugues, Denis Martinvalet, Bénédicte Manoury, Nicolas Demaurex
Antigen cross-presentation by dendritic cells (DC) stimulates cytotoxic T cell activation to promote immunity to intracellular pathogens, viruses and cancer. Phagocytosed antigens generate potent T cell responses, but the signalling and trafficking pathways regulating their cross-presentation are unclear. Here, we show that ablation of the store-operated-Ca2+-entry regulator STIM1 in mouse myeloid cells impairs cross-presentation and DC migration in vivo and in vitro. Stim1 ablation reduces Ca2+ signals, cross-presentation, and chemotaxis in mouse bone-marrow-derived DCs without altering cell differentiation, maturation or phagocytic capacity...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29163781/synj2bp-promotes-the-degradation-of-pten-through-the-lysosome-pathway-and-enhances-breast-tumor-metastasis-via-pi3k-akt-snai1-signaling
#15
Miao Wang, Huijian Wu, Shujing Li, Zhaowei Xu, Xiahui Li, Yangyang Yang, Bowen Li, Yanan Li, Jing Guo, Huan Chen
SYNJ2BP plays an important role in breast cancer metastasis. However, the molecular mechanism associated with the function of SYNJ2BP in metastasis remains unclear. In this study, we investigated the role of SYNJ2BP in tumor metastasis and established the associated underlying mechanism. Over-expression of SYNJ2BP promoted both cell migration and invasion. In contrast, silencing SYNJ2BP caused the suppression of cell migration and invasion. SYNJ2BP increased the levels of phosphorylation for AKT and GSK3β, which could be inhibited by the PI3K inhibitor, LY294002, and the GSK3β inhibitor, LiCl, and regulated the accumulation of SNAI1 in the nucleus and the expression of the SNAI1 target gene, E-cadherin (EMT marker)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158820/ph-sensitive-nano-complexes-overcome-drug-resistance-and-inhibit-metastasis-of-breast-cancer-by-silencing-akt-expression
#16
Jieying Yin, Tianqun Lang, Dongmei Cun, Zhong Zheng, Yan Huang, Qi Yin, Haijun Yu, Yaping Li
The therapy of breast cancer is encumbered by drug resistance and metastasis, which can be due to a defective PI3K/AKT/mTOR signaling pathway. This study was aimed at improving the anti-cancer effect of the chemotherapeutic agent paclitaxel (PTX) on the drug resistant and metastatic breast cancer by co-delivering PTX and a siRNA, siAkt, directed at silencing the Akt expression. Methods: The pH-sensitive amphiphilic polymer, poly [(1,4-butanediol)-diacrylate-β-N, N-diisopropylethylenediamine]-polyethyleneimine (BDP) was synthesized...
2017: Theranostics
https://www.readbyqxmd.com/read/29149721/biological-safety-and-tissue-distribution-of-16-mercaptohexadecyl-trimethylammonium-bromide-modified-cationic-gold-nanorods
#17
Monika Zarska, Michal Sramek, Filip Novotny, Filip Havel, Andrea Babelova, Blanka Mrazkova, Oldrich Benada, Milan Reinis, Ivan Stepanek, Kamil Musilek, Jiri Bartek, Monika Ursinyova, Ondrej Novak, Rastislav Dzijak, Kamil Kuca, Jan Proska, Zdenek Hodny
The exceptionally high cellular uptake of gold nanorods (GNRs) bearing cationic surfactants makes them a promising tool for biomedical applications. Given the known specific toxic and stress effects of some preparations of cationic nanoparticles, the purpose of this study was to evaluate, in an in vitro and in vivo in mouse, the potential harmful effects of GNRs coated with (16-mercaptohexadecyl)trimethylammonium bromide ((MTAB)GNRs). Interestingly, even after cellular accumulation of high amounts of (MTAB)GNRs sufficient for induction of photothermal effect, no genotoxicity (even after longer-term accumulation), induction of autophagy, destabilization of lysosomes (dominant organelles of their cellular destination), alterations of actin cytoskeleton, or in cell migration could be detected in vitro...
November 1, 2017: Biomaterials
https://www.readbyqxmd.com/read/29140069/dual-functions-of-cyclometalated-iridium-iii-complexes-anti-metastasis-and-lysosome-damaged-photodynamic-therapy
#18
Fang-Xin Wang, Mu-He Chen, Yan-Nan Lin, Hang Zhang, Cai-Ping Tan, Liang-Nian Ji, Zongwan Mao
Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can inhibit several cancerous processes including cell migration, invasion, colony formation and angiogenesis effectively. Interestingly, they show much higher singlet oxygen quantum yield in acidic solution than in neutral solution. Upon irradiation at 425 nm with low energy (1.2 J·cm(-2)), they can induce apoptosis through lysosomal damage, evaluation of ROS level and activation of caspase-3/7...
November 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29116364/low-density-lipoprotein-receptor-related-protein-1-couples-%C3%AE-1-integrin-activation-to-degradation
#19
Lukasz Wujak, Ralph T Böttcher, Oleg Pak, Helena Frey, Elie El Agha, Ying Chen, Sigrid Schmitt, Saverio Bellusci, Liliana Schaefer, Norbert Weissmann, Reinhard Fässler, Malgorzata Wygrecka
Low density lipoprotein receptor-related protein (LRP) 1 modulates cell adhesion and motility under normal and pathological conditions. Previous studies documented that LRP1 binds several integrin receptors and mediates their trafficking to the cell surface and endocytosis. However, the mechanism by which LRP1 may regulate integrin activation remains unknown. Here we report that LRP1 promotes the activation and subsequent degradation of β1 integrin and thus supports cell adhesion, spreading, migration and integrin signaling on fibronectin...
November 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29115486/antitumor%C3%A2-and-apoptosis%C3%A2-inducing-effects-of-pomolic-acid-against-sk%C3%A2-mel%C3%A2-2-human-malignant-melanoma-cells-are-mediated-via-inhibition-of-cell-migration-and-sub%C3%A2-g1-cell-cycle-arrest
#20
Tian-Hang Li, Hong-Xia Yan
Malignant melanoma is the leading cause of mortality among the skin‑associated diseases because of its highly metastatic nature and lethality. The aim of the present study was to evaluate antitumor and apoptosis effects of pomolic acid, a pentacyclic triterpene, against SK‑MEL‑2 human malignant melanoma cells. Its effect on cell migration and cell cycle arrest were also studied. An MTT assay was used to assess the cell cytotoxicity effects induced by pomolic acid. Fluorescence microscopy using acridine orange/propidium iodide and Hoechst 33342 staining, along with transmission electron microscopy (TEM), was used to study the effects of pomolic acid on apoptosis induction in these cells...
November 6, 2017: Molecular Medicine Reports
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