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Lysosome and migration

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https://www.readbyqxmd.com/read/29051140/fgd5-faciogenital-dysplasia-5-regulates-vegf-vascular-endothelial-growth-factor-a-receptor-2-coupling-to-pi3-phosphoinositide-3-kinase-and-receptor-recycling
#1
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 (3D) in vitro model...
October 19, 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
#2
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
#3
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...
October 16, 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
#4
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
https://www.readbyqxmd.com/read/28983581/bioinformatics-analysis-of-fibroblasts-exposed-to-tgf%C3%A2-%C3%AE-at-the-early-proliferation-phase-of-wound-repair
#5
Bobin Mi, Guohui Liu, Wu Zhou, Huijuan Lv, Kun Zha, Yi Liu, Qipeng Wu, Jing Liu
The aim of the current study was to identify gene signatures during the early proliferation stage of wound repair and the effect of TGF‑β on fibroblasts and reveal their potential mechanisms. The gene expression profiles of GSE79621 and GSE27165 were obtained from GEO database. Differentially expressed genes (DEGs) were identified using Morpheus and co‑expressed DEGs were selected using Venn Diagram. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool...
September 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28938624/addition-of-2-ethylamino-acetonitrile-group-to-nitroxoline-results-in-significantly-improved-anti-tumor-activity-in-vitro-and-in-vivo
#6
Ana Mitrović, Izidor Sosič, Špela Kos, Urša Lampreht Tratar, Barbara Breznik, Simona Kranjc, Bojana Mirković, Stanislav Gobec, Tamara Lah, Gregor Serša, Janko Kos
Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo. In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28924047/endothelial-rab7-gtpase-mediates-tumor-growth-and-metastasis-in-lysosomal-acid-lipase-deficient-mice
#7
Ting Zhao, Xinchun Ding, Cong Yan, Hong Du
Tumors depend on their microenvironment for sustained growth, invasion and metastasis. In this environment, endothelial cells (ECs) are an important stromal cell type interacting with malignant cells to facilitate tumor angiogenesis and cancer cell extravasation. Of note, lysosomal acid lipase (LAL) deficiency facilitates melanoma growth and metastasis. ECs from LAL-deficient (lal-/-) mice possess enhanced proliferation, migration, and permeability of inflammatory cells by activating the mammalian target of rapamycin (mTOR) pathway...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28888937/low-density-lipoprotein-receptor-class-a-domain-containing-4-ldlrad4-promotes-tumorigenesis-of-hepatic-cancer-cells
#8
Zhenxing Liu, Xin Huo, Shuang Zhao, Jingjing Yang, Wenxia Shi, Lei Jing, Wei Li, Yuyin Li, Long Ma, Yingtang Gao, Aipo Diao
LDLRAD4 was previously identified and shown to be connected with psychiatric disorders. The structure of LDLRAD4 protein is similar to that of TMEPAI protein, which is overexpressed in many tumors. However, it is still unknown whether LDLRAD4 is involved in tumorigenesis. In this study, the potential role of LDLRAD4 in tumorigenesis was investigated. LDLRAD4 is elevated in hepatic cancer cells and tumor tissues, and expression of LDLRAD4 promotes hepatic cancer cell HepG2 and SMMC-7721 proliferation and migration...
September 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28884480/blood-monocytes-sample-melana-mart1-antigen-for-long-lasting-cross-presentation-to-cd8-t-cells-after-differentiation-into-dendritic-cells
#9
Florence Faure, Mabel Jouve, Isabelle Lebhar-Peguillet, Charlotte Sadaka, Fernando Sepulveda, Olivier Lantz, Stefano Berre, Raphael Gaudin, Silvia Sánchez-Ramón, Sebastian Amigorena
Human blood monocytes are very potent to take up antigens. Like macrophages in tissue, they efficiently degrade exogenous protein and are less efficient than dendritic cells (DCs) at cross-presenting antigens to CD8(+) T cells. Although it is generally accepted that DCs take up tissue antigens and then migrate to lymph nodes to prime T cells, the mechanisms of presentation of antigens taken up by monocytes are poorly documented so far. In the present work, we show that monocytes loaded in vitro with MelanA long peptides retain the capacity to stimulate antigen-specific CD8(+) T cell clones after 5 days of differentiation into monocytes-derived dendritic cells (MoDCs)...
September 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28883791/proteasome-inhibitor-ysy01a-abrogates-constitutive-stat3-signaling-via-down-regulation-of-gp130-and-jak2-in-human-a549-lung-cancer-cells
#10
Wei Huang, Xia Yuan, Ting Sun, Shujie Fan, Jun Wang, Quan Zhou, Wei Guo, Fuxiang Ran, Zemei Ge, Huayu Yang, Runtao Li, Jingrong Cui
Proteasome inhibition interfering with many cell signaling pathways has been extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor YSY01A is a novel agent that has shown remarkable anti-tumor effects; however, its mechanisms of action are not fully understood. Here we report that YSY01A is capable of suppressing cancer cell survival by induction of apoptosis. Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via proteasome-independent degradation of gp130 and JAK2, but not transcriptional regulation, in human A549 non-small cell lung cancer cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28852060/fmnl2-and-3-regulate-golgi-architecture-and-anterograde-transport-downstream-of-cdc42
#11
Frieda Kage, Anika Steffen, Adolf Ellinger, Carmen Ranftler, Christian Gehre, Cord Brakebusch, Margit Pavelka, Theresia Stradal, Klemens Rottner
The Rho-family small GTPase Cdc42 localizes at plasma membrane and Golgi complex and aside from protrusion and migration operates in vesicle trafficking, endo- and exocytosis as well as establishment and/or maintenance of cell polarity. The formin family members FMNL2 and -3 are actin assembly factors established to regulate cell edge protrusion during migration and invasion. Here we report these formins to additionally accumulate and function at the Golgi apparatus. As opposed to lamellipodia, Golgi targeting of these proteins required both their N-terminal myristoylation and the interaction with Cdc42...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842335/concurrently-suppressing-multidrug-resistance-and-metastasis-of-breast-cancer-by-co-delivery-of-paclitaxel-and-honokiol-with-ph-sensitive-polymeric-micelles
#12
Ziqi Wang, Xinru Li, Dishi Wang, Yang Zou, Xiaoyou Qu, Chuyu He, Yunqiang Deng, Yao Jin, Yuanhang Zhou, Yanxia Zhou, Yan Liu
To concurrently suppress multidrug resistance (MDR) and metastasis of breast cancer cells, paclitaxel (PTX) and honokiol (HNK) were coencapsulated into pH-sensitive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (PEOz-PLA). The physicochemical properties of dual drug-loaded PEOz-PLA micelles were characterized in size, drug loading and in vitro release. The efficiency of MDR reversal for the micelles was testified by synergetic enhancement of cytotoxicity and uptake by MCF-7/ADR cells...
August 28, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28789934/targeting-calpains-a-novel-immunomodulatory-approach-for-microbial-infections
#13
REVIEW
Vijay Kumar, Ahmad Ali
Calpains are a family of Ca(2+) dependent cytosolic non-lysosomal proteases with well conserved cysteine-rich domains for enzymatic activity. Due to their functional dependency on Ca(2+) concentrations, they are involved in various cellular processes that are regulated by intracellular ca(2+) concentration (i.e. embryo development, cell development and migration, maintenance of cellular architecture and structure etc.). Calpains are widely studied proteases in mammalian (i.e. mouse and human) physiology and pathophysiology due to their ubiquitous presence...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28754879/addition-of-2-ethylamino-acetonitrile-group-to-nitroxoline-results-in-significantly-improved-anti-tumor-activity-in-vitro-and-in-vivo
#14
Ana MitroviÄ, Izidor SosiÄ, Špela Kos, Urša Lampreht Tratar, Barbara Breznik, Simona Kranjc, Bojana MirkoviÄ, Stanislav Gobec, Tamara Lah, Maja Ä emaÅ Ar, Gregor Serša, Janko Kos
Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo. In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751541/downregulation-of-cavin-1-expression-via-increasing-caveolin-1-degradation-prompts-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-in-balloon-injury-induced-neointimal-hyperplasia
#15
Li-Jun Zhou, Xue-Ying Chen, Shui-Ping Liu, Lin-Lin Zhang, Ya-Nan Xu, Pan-Wei Mu, Deng-Feng Geng, Zhi Tan
BACKGROUND: Percutaneous coronary intervention has been widely used in the treatment of ischemic heart disease, but vascular restenosis is a main limitation of percutaneous coronary intervention. Our previous work reported that caveolin-1 had a key functional role in intimal hyperplasia, whereas whether Cavin-1 (another important caveolae-related protein) was involved is still unknown. Therefore, we will investigate the effect of Cavin-1 on neointimal formation. METHODS AND RESULTS: Balloon injury markedly reduced Cavin-1 protein and enhanced ubiquitin protein expression accompanied with neointimal hyperplasia in injured carotid arteries, whereas Cavin-1 mRNA had no change...
July 27, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28745237/anethole-inhibits-the-proliferation-of-human-prostate-cancer-cells-via-induction-of-cell-cycle-arrest-and-apoptosis
#16
Ayman Ibrahim Elkady
BACKGROUND: Prostate cancer-associated mortality is increasing at an alarming rate, which highlights the inevitability for unearthing novel agent for the management of this disease. Anethole, a major constituent of Foeniculum vulgare (fennel) essential oil, is widely used in folk medicine; it possesses anti-oxidant, anti-inflammatory, anti-proliferative and tumoricidal potentialities. OBJECTIVE: The current research was conducted to assess the impact of anethole on prostate cancer cell line, PC-3, and to delineate the molecular mechanism of action...
July 25, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28735522/characterization-of-the-role-of-rilp-in-cell-migration
#17
Azzurra Margiotta, Cinzia Progida, Oddmund Bakke, Cecilia Bucci
Rab-interacting lysosomal protein (RILP) is a regulator of late stages of endocytosis. Recent work proved that depletion of RILP promotes migration of breast cancer cells in wound healing assay, whereas its overexpression influences re-arrangements of actin cytoskeleton. Here, we further characterized the role of RILP in cell migration by analyzing several aspects of this process. We showed that RILP is fundamental also for migration of lung cancer cells regulating cell velocity. RILP silencing did not affect Golgi apparatus nor microtubules reorientation during migration...
May 31, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28733362/loss-of-cln5-causes-altered-neurogenesis-in-a-mouse-model-of-a-childhood-neurodegenerative-disorder
#18
Ekaterina Savchenko, Yajuvinder Singh, Henna Konttinen, Katarina Lejavova, Laura Mediavilla Santos, Alexandra Grubman, Virve Kärkkäinen, Velta Keksa-Goldsteine, Nikolay Naumenko, Pasi Tavi, Anthony R White, Tarja Malm, Jari Koistinaho, Katja M Kanninen
Neural stem/progenitor cells (NPCs) generate new neurons in the brain throughout an individual's lifetime in an intricate process called neurogenesis. Neurogenic alterations are a common feature of several adult-onset neurodegenerative diseases. The neuronal ceroid lipofuscinoses (NCLs) are the most common group of inherited neurodegenerative diseases that mainly affect children. Pathological features of the NCLs include accumulation of lysosomal storage material, neuroinflammation and neuronal degeneration, yet the exact cause of this group of diseases remains poorly understood...
September 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28717168/dynamics-and-function-of-cxcr4-in-formation-of-the-granule-cell-layer-during-hippocampal-development
#19
Yuka Mimura-Yamamoto, Hiroshi Shinohara, Taichi Kashiwagi, Toru Sato, Seiji Shioda, Tatsunori Seki
In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708385/chloroquine-modified-hydroxyethyl-starch-as-a-polymeric-drug-for-cancer-therapy
#20
Richard Sleightholm, Bin Yang, Fei Yu, Ying Xie, David Oupický
Hydroxyethyl starch (HES) is a clinically used polysaccharide colloidal plasma volume expander. The goal of this study was to synthesize HES modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer (PC) cells. HES was conjugated with HCQ using a simple carbonyldiimidazole coupling to prepare Chloroquine-modified HES (CQ-HES). CQ-HES with various degrees of HCQ substitution were synthesized and characterized. Atomic force microscopy was used to demonstrate a pH-dependent assembly of CQ-HES into well-defined nanoparticles...
July 14, 2017: Biomacromolecules
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