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Lysosome and migration

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https://www.readbyqxmd.com/read/29187366/cell-confluence-regulates-claudin-2-expression-possible-role-for-zo-1-and-rac
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/29113338/mir-23a-modulates-x-linked-inhibitor-of-apoptosis-mediated-autophagy-in-human-luminal-breast-cancer-cell-lines
#10
Ping Chen, Yin-Huan He, Xing Huang, Si-Qi Tao, Xiao-Nan Wang, Hong Yan, Ke-Shuo Ding, Peter E Lobie, Wen-Yong Wu, Zheng-Sheng Wu
Autophagy is a conserved multi-step lysosomal process that is induced by diverse stimuli including cellular nutrient deficiency. X-linked inhibitor of apoptosis (XIAP) promotes cell survival and recently has been demonstrated to suppress autophagy. Herein, we examined regulation of XIAP-mediated autophagy in breast cancer cells and determined the underlying molecular mechanism. To investigate this process, autophagy of breast cancer cells was induced by Earle's balanced salt solution (EBSS). We observed discordant expression of XIAP mRNA and protein in the autophagic process induced by EBSS, suggesting XIAP may be regulated at a post-transcriptional level...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113270/cleistanthin-a-inhibits-the-invasion-and-metastasis-of-human-melanoma-cells-by-inhibiting-the-expression-of-matrix-metallopeptidase-2-and-9
#11
Sheng Pan, Hengji Cai, Lixiong Gu, Shuanglin Cao
It has been demonstrated that numerous types of metastatic cancer overexpress vacuolar-type H(+) (V)-ATPases. It may be possible to inhibit the growth and metastasis of human cancer cells by inhibiting V-ATPases. It was previously reported that diphyllin, a novel V-ATPase inhibitor, can inhibit the migration and invasion of SGC7901 human gastric cancer cells; however, the effects of cleistanthin A (CA), a diphyllin glycoside, on melanoma cells has not been demonstrated. The present study aimed to investigate the effect of CA as a V-ATPase inhibitor and its effects on the invasion and metastasis of A375 cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29108920/correlation-of-lysosome-associated-protein-transmembrane-4%C3%AE-gene-overexpression-with-the-malignant-phenotypes-of-hepatocellular-carcinoma
#12
Hongying Su, Tao Xu, Xiongfei Huang, Shengbing Zang, Bin Wang, Yang Huang, Jingfeng Liu, Aimin Huang
Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal malignancies, for which hepatitis B virus (HBV) chronic infection constitutes a major risk factor. The lysosome-associated protein transmembrane-4 β gene (LAPTM4B) is a recently identified gene that was found to be overexpressed in several types of cancer. However, the role of LAPTM4B in HCC tumorigenesis and progression has not been clearly determined. The present study demonstrated that the mRNA as well as the protein levels of LAPTM4B were significantly upregulated in HCC specimens...
October 7, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29107116/mitophagy-and-the-release-of-inflammatory-cytokines
#13
REVIEW
James Harris, Nadia Deen, Shahrzad Zamani, Md Abul Hasnat
Mitophagy is a selective form of autophagy in which damaged or dysfunctional mitochondria are specifically targeted by autophagosomes for lysosomal degradation. Studies have demonstrated that loss of autophagy/mitophagy can lead to a build-up of cytosolic reactive oxygen species and mitochondrial DNA, which can, in turn, activate immune signalling pathways that ultimately lead to the releases of inflammatory cytokines, including IL-1α, IL-1β, IL-18 and macrophage migration inhibitory factor (MIF). Moreover, release of these cytokines can subsequently promote the release of others, including IL-23 and IL-17...
October 26, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29100552/cooperative-antitumor-activities-of-carnosic-acid-and-trastuzumab-in-erbb2-breast-cancer-cells
#14
Carolina D'Alesio, Grazia Bellese, Maria Cristina Gagliani, Cinzia Aiello, Elena Grasselli, Gianluca Marcocci, Angela Bisio, Sara Tavella, Tiziana Daniele, Katia Cortese, Patrizio Castagnola
BACKGROUND: ERBB2 is overexpressed in up to 20-30% of human breast cancers (BCs), and it is associated with aggressive disease. Trastuzumab (Tz), a humanized monoclonal antibody, improves the prognosis associated with ERBB2-amplified BCs. However, the development of resistance remains a significant challenge. Carnosic acid (CA) is a diterpene found in rosemary and sage, endowed with anticancer properties. In this in vitro study, we have investigated whether Tz and CA have cooperative effects on cell survival of ERBB2 overexpressing (ERBB2(+)) cells and whether CA might restore Tz sensitivity in Tz-resistant cells...
November 3, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29079589/lysosome-signaling-controls-the-migration-of-dendritic-cells
#15
Marine Bretou, Pablo J Sáez, Doriane Sanséau, Mathieu Maurin, Danielle Lankar, Melanie Chabaud, Carmine Spampanato, Odile Malbec, Lucie Barbier, Shmuel Muallem, Paolo Maiuri, Andrea Ballabio, Julie Helft, Matthieu Piel, Pablo Vargas, Ana-Maria Lennon-Duménil
Dendritic cells (DCs) patrol their environment by linking antigen acquisition by macropinocytosis to cell locomotion. DC activation upon bacterial sensing inhibits macropinocytosis and increases DC migration, thus promoting the arrival of DCs to lymph nodes for antigen presentation to T cells. The signaling events that trigger such changes are not fully understood. We show that lysosome signaling plays a critical role in this process. Upon bacterial sensing, lysosomal calcium is released by the ionic channel TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1), which activates the actin-based motor protein myosin II at the cell rear, promoting fast and directional migration...
October 27, 2017: Science Immunology
https://www.readbyqxmd.com/read/29059167/loss-of-rhoa-promotes-skin-tumor-formation-and-invasion-by-upregulation-of-rhob
#16
A García-Mariscal, H Li, E Pedersen, K Peyrollier, K M Ryan, A Stanley, F Quondamatteo, C Brakebusch
Cellular movement is controlled by small GTPases, such as RhoA. Although migration is crucial for cancer cell invasion, the specific role of RhoA in tumor formation is unclear. Inducing skin tumors in mice with a keratinocyte-restricted loss of RhoA, we observed increased tumor frequency, growth and invasion. In vitro invasion assays revealed that in the absence of RhoA cell invasiveness is increased in a Rho-associated protein kinase (ROCK) activation and cell contraction-dependent manner. Surprisingly, loss of RhoA causes increased Rho signaling via overcompensation by RhoB because of reduced lysosomal degradation of RhoB in Gamma-aminobutyric acid receptor-associated protein (GABARAP)+ autophagosomes and endosomes...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29051140/fgd5-regulates-vegf-receptor-2-coupling-to-pi3-kinase-and-receptor-recycling
#17
Maikel A Farhan, Abul K Azad, Nicolas Touret, Allan G Murray
OBJECTIVE: VEGF (vascular endothelial growth factor-A) signaling to the endothelial cell (EC) through VEGFR2 (VEGF receptor-2) is the principal cue driving new blood vessel formation. FGD5 (faciogenital dysplasia-5)-a Rho-family guanine nucleotide exchange factor-is selectively expressed in EC. Deficiency of FGD5 is embryonically lethal in mice and perturbs angiogenesis and VEGF signal transduction. However, the mechanism of FGD5 regulation of VEGF signaling is poorly understood. APPROACH AND RESULTS: Angiogenic sprouting and EC cytoskeletal remodeling were evaluated in a 3-dimensional in vitro model...
December 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29048615/overexpression-of-rab34-correlates-with-poor-prognosis-and-tumor-progression-in-hepatocellular-carcinoma
#18
Jianwu Wu, Yijie Lu, Ancheng Qin, Zhiming Qiao, Xinwei Jiang
RAB34, a protein belonging to the RAB family, is involved in protein transport, repositioning of lysosomes and activation of micropinocytosis. However, few studies have reported its function in human epithelial cancers. Immunohistochemistry (IHC) and western blotting were used to detect expression of RAB34 at the tissue and cell levels. Cell Counting Kit-8 (CCK-8), EDU assay and flow cytometry were used for analyzing cell proliferation. Transwell and scratch wound healing assays were used for assessing cell migration ability...
September 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29038303/f-actin-reorganization-by-v-atpase-inhibition-in-prostate-cancer
#19
Yamhilette Licon-Munoz, Vera Michel, Colleen A Fordyce, Karlett J Parra
The vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and its inhibition triggers numerous stress responses. However, the cellular mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly metastatic PCa. V-ATPase inhibitors impaired endo-lysosomal pH, vesicle trafficking, migration, and invasion. V-ATPase accrual in the Golgi and recycling endosomes suggests that traffic of internalized membrane vesicles back to the plasma membrane was particularly impaired...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29024694/cathepsin-d-non-proteolytically-induces-proliferation-and-migration-in-human-omental-microvascular-endothelial-cells-via-activation-of-the-erk1-2-and-pi3k-akt-pathways
#20
Md Zahidul I Pranjol, Nicholas J Gutowski, Michael Hannemann, Jacqueline L Whatmore
Epithelial ovarian cancer (EOC) frequently metastasises to the omentum, a process that requires pro-angiogenic activation of human omental microvascular endothelial cells (HOMECs) by tumour-secreted factors. We have previously shown that ovarian cancer cells secrete a range of factors that induce pro-angiogenic responses e.g. migration, in HOMECs including the lysosomal protease cathepsin D (CathD). However, the cellular mechanism by which CathD induces these cellular responses is not understood. The aim of this study was to further examine the pro-angiogenic effects of CathD in HOMECs i...
October 10, 2017: Biochimica et Biophysica Acta
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