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Macropinocytosis

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https://www.readbyqxmd.com/read/29152126/extracellular-atp-as-an-energy-and-phosphorylating-molecule-induces-different-types-of-drug-resistances-in-cancer-cells-through-atp-internalization-and-intracellular-atp-level-increase
#1
Xuan Wang, Yunsheng Li, Yanrong Qian, Yanyang Cao, Pratik Shriwas, Haiyun Zhang, Xiaozhuo Chen
Cancer cells are able to uptake extracellular ATP (eATP) via macropinocytosis to elevate intracellular ATP (iATP) levels, enhancing their survival in drug treatment. However, the involved drug resistance mechanisms are unknown. Here we investigated the roles of eATP as either an energy or a phosphorylating molecule in general drug resistance mediated by ATP internalization and iATP elevation. We report that eATP increased iATP levels and promoted drug resistance to various tyrosine kinase inhibitors (TKIs) and chemo-drugs in human cancer cell lines of five cancer types...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150487/dynamin-inhibitors-block-mtorc1-activation-by-amino-acids-independently-of-dynamin
#2
Persaud Avinash, Cormerais Yann, Pouyssegur Jacques, Rotin Daniela
mTORC1 plays a critical role in protein synthesis and cell proliferation and growth. It is activated by growth factors and amino acids, including essential amino acid (EAA), such as Leu; Leu enters cells via the Leu transporter LAT1-4F2hc and potentially via endocytosis. Here we investigated the contribution of the different routes of Leu entry into cells to mTORC1 activation using pharmacological inhibitors and cells that lack LAT1 or dynamin1/2/3. Our results show that LAT1 is the major route of Leu entry into cells and mTORC1 activation (∼70%), while dynamin-dependent endocytosis and macropinocytosis contribute minimally to both (5-15%)...
November 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29119997/dimeric-camptothecin-loaded-rgd-modified-targeted-cationic-polypeptide-based-micelles-with-high-drug-loading-capacity-and-redox-responsive-drug-release-capability
#3
Zhaopei Guo, Xingzhi Zhou, Mengze Xu, Huayu Tian, Xuesi Chen, Meiwan Chen
Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ε-carbobenzoxy-l-lysine (ε-Lys(Z)) and l-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide...
November 9, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29119228/macropinocytosis-mtorc1-and-cellular-growth-control
#4
REVIEW
Sei Yoshida, Regina Pacitto, Ken Inoki, Joel Swanson
The growth and proliferation of metazoan cells are driven by cellular nutrient status and by extracellular growth factors. Growth factor receptors on cell surfaces initiate biochemical signals that increase anabolic metabolism and macropinocytosis, an actin-dependent endocytic process in which relatively large volumes of extracellular solutes and nutrients are internalized and delivered efficiently into lysosomes. Macropinocytosis is prominent in many kinds of cancer cells, and supports the growth of cells transformed by oncogenic K-Ras...
November 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29117102/mechanisms-of-entry-and-endosomal-pathway-of-african-swine-fever-virus
#5
REVIEW
Elena G. Sánchez, Daniel Pérez-Núñez, Yolanda Revilla
African Swine Fever Virus (ASFV) causes a serious swine disease that is endemic in Africa and Sardinia and presently spreading in Russia and neighboring countries, including Poland and recently, the Czech Republic. This uncontrolled dissemination is a world-wide threat, as no specific protection or vaccine is available. ASFV is a very complex icosahedral, enveloped virus about 200 nm in diameter, which infects several members of pigs. The virus enters host cells by receptor-mediated endocytosis that depends on energy, vacuolar pH and temperature...
November 8, 2017: Vaccines
https://www.readbyqxmd.com/read/29115333/an-apolipoprotein-enriched-biomolecular-corona-switches-the-cellular-uptake-mechanism-and-trafficking-pathway-of-lipid-nanoparticles
#6
L Digiacomo, F Cardarelli, D Pozzi, S Palchetti, M A Digman, E Gratton, A L Capriotti, M Mahmoudi, G Caracciolo
Following exposure to biological milieus (e.g. after systemic administration), nanoparticles (NPs) get covered by an outer biomolecular corona (BC) that defines many of their biological outcomes, such as the elicited immune response, biodistribution, and targeting abilities. In spite of this, the role of BC in regulating the cellular uptake and the subcellular trafficking properties of NPs has remained elusive. Here, we tackle this issue by employing multicomponent (MC) lipid NPs, human plasma (HP) and HeLa cells as models for nanoformulations, biological fluids, and target cells, respectively...
November 16, 2017: Nanoscale
https://www.readbyqxmd.com/read/29113042/ph-responsive-micelle-based-cytoplasmic-delivery-system-for-induction-of-cellular-immunity
#7
Eiji Yuba, Naoki Sakaguchi, Yuhei Kanda, Maiko Miyazaki, Kazunori Koiwai
(1) Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC) and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability...
November 4, 2017: Vaccines
https://www.readbyqxmd.com/read/29106503/induction-of-non-apoptotic-programmed-cell-death-by-oncogenic-ras-in-human-epithelial-cells-and-its-suppression-by-myc-overexpression
#8
Kasumi Dendo, Takashi Yugawa, Tomomi Nakahara, Shin-Ichi Ohno, Naoki Goshima, Hirofumi Arakawa, Tohru Kiyono
Oncogenic mutations of RAS genes, found in about 30% of human cancers, are considered to play important roles in cancer development. However, oncogenic RAS can also induce senescence in mouse and human normal fibroblasts. In some cell lines, oncogenic RAS has been reported to induce non-apoptotic programed cell death (PCD). Here, we investigated effects of oncogenic RAS expression in several types of normal human epithelial cells. Oncogenic RAS but not wild-type RAS stimulated macropinocytosis with accumulation of large phase-lucent vacuoles in the cytoplasm, subsequently leading to cell death which was indistinguishable from a recently proposed new type of PCD, methuosis...
November 2, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29102889/identification-of-the-caveolae-raft-mediated-endocytosis-as-the-primary-entry-pathway-for-aquareovirus
#9
Fuxian Zhang, Hong Guo, Jie Zhang, Qingxiu Chen, Qin Fang
Grass carp reovirus (GCRV), a member of the Aquareovirus genus in the Reoviridae family, is considered the most pathogenic aquareovirus. However, its productive viral entry pathways remain largely unclear. Using a combination of quantum dot (QD)-based live-virus tracking and biochemical assays, we found that extraction of cellular membrane cholesterol with methyl-β-cyclodextrin (MβCD) and nystatin strongly inhibited the internalization of GCRVs, and supplementation with cholesterol restored viral infection...
November 2, 2017: Virology
https://www.readbyqxmd.com/read/29097619/targeting-the-lysosome-for-cancer-therapy
#10
Christina G Towers, Andrew Thorburn
Lysosomes are the recycling centers of the cell where organelles and proteins are degraded during autophagy and macropinocytosis; they also serve as signaling hubs that control the activity of mTORC1. In this issue, Rebecca and colleagues report the development of a new type of lysosomal inhibitor for cancer therapy that can inhibit multiple lysosomal activities that are needed for tumor cell survival and growth. Cancer Discov; 7(11); 1218-20. ©2017 AACRSee related article by Rebecca et al., p. 1266.
November 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29093026/differential-ability-of-pro-inflammatory-and-anti-inflammatory-macrophages-to-perform-macropinocytosis
#11
Dar'ya S Redka, Michael Gütschow, Sergio Grinstein, Johnathan Canton
Macropinocytosis mediates the uptake of antigens and of nutrients that dictate the regulation of cell growth by mechanistic target of rapamycin complex 1 (mTORC1). Because these functions differ in pro-inflammatory and anti-inflammatory macrophages, we compared the macropinocytic ability of two extreme polarization states. We found that anti-inflammatory macrophages perform vigorous macropinocytosis constitutively, while pro-inflammatory cells are virtually inactive. The total cellular content of Rho-family GTPases was higher in anti-inflammatory cells, but this disparity failed to account for the differential macropinocytic activity...
November 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29079589/lysosome-signaling-controls-the-migration-of-dendritic-cells
#12
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/29072633/endocytosis-of-corn-oil-caseinate-emulsions-in-vitro-impacts-of-droplet-sizes
#13
Yuting Fan, Yuzhu Zhang, Wally Yokoyama, Jiang Yi
The relative uptake and mechanisms of lipid-based emulsions of three different particle diameters by Caco-2 cells were studied. The corn oil-sodium caseinate emulsions showed little or no cytotoxicity even at 2 mg/mL protein concentration for any of the three droplet size emulsions. Confocal laser scanning microscopy (CLSM) of Nile red containing emulsions showed that the lipid-based emulsions were absorbed by Caco-2 cells. A negative correlation between the mean droplet size and cellular uptake was observed...
October 26, 2017: Nanomaterials
https://www.readbyqxmd.com/read/29071179/novel-hyaluronic-acid-conjugates-for-dual-nuclear-imaging-and-therapy-in-cd44-expressing-tumors-in-mice-in-vivo
#14
Ravindra Dhar Dubey, Rebecca Klippstein, Julie Tzu-Wen Wang, Naomi Hodgins, Kuo-Ching Mei, Jane Sosabowski, Robert C Hider, Vincenzo Abbate, Prem N Gupta, Khuloud T Al-Jamal
Hyaluronic acid, a natural CD44 receptor ligand, has attracted attention in the past years as a macromolecular delivery of anticancer agents to cancer. At the same time, the clinical applications of Gemcitabine (Gem) have been hindered by its short biological half-life, high dose and development of drug resistance. This work reports the synthesis of a hyaluronic acid (HA) conjugate for nuclear imaging, and in vivo Gem delivery to CD44-expressing solid tumors in mice. HA was individually conjugated, via amide coupling, to Gem (HA-Gem), 4'-(aminomethyl)fluorescein hydrochloride (HA-4'-AMF) or tris(hydroxypyridinone) amine (HA-THP) for cancer therapy, in vitro tracking or single photon emission computed tomography/computed tomography (SPECT/CT) imaging, respectively...
2017: Nanotheranostics
https://www.readbyqxmd.com/read/29058908/intracellular-fate-of-nanoparticles-with-polydopamine-surface-engineering-and-a-novel-strategy-for-exocytosis-inhibiting-lysosome-impairment-based-cancer-therapy
#15
Li Ding, Xianbing Zhu, Yiling Wang, Bingyang Shi, Xiang Ling, Houjie Chen, Wenhao Nan, Austin Barrett, Zilei Guo, Wei Tao, Jun Wu, Xiaojun Shi
Polydopamine (PDA) coating as a bioinspired strategy for nanoparticles (NPs) has been extensively applied in cancer theranostics. However, a cellular-level understanding of nano-biointeraction of these PDA-coated NPs (PDNPs), which drives the fate of them and acts as a critical step to determine their efficacy, still remains unknown. Herein, we utilized the representative mesoporous silica NPs (MSNs) to be coated with PDA and study their nano-bioactivities in cancer cells. HeLa cell line was utilized as a model in this study...
October 27, 2017: Nano Letters
https://www.readbyqxmd.com/read/29053471/pegylated-anticancer-carbon-nanotubes-complex-targeting-mitochondria-of-lung-cancer-cells
#16
Sang-Woo Kim, Yeon Kyung Lee, Jong Yeon Lee, Jeong Hee Hong, Dongwoo Khang
Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube (CNT)-ABT737 nanodrug that improves the mitochondrial targeting of lung cancer cells. The polyethylene glycol-coated CNT-ABT737 nanodrug internalized into the early endosomes via macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal escape and delivered into the mitochondria...
October 20, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29050600/evaluation-of-disulfide-bond-conjugated-lmwsc-g-bpei-as-non-viral-vector-for-low-cytotoxicity-and-efficient-gene-delivery
#17
Gyeong-Won Jeong, Jae-Woon Nah
For efficient gene delivery, non-viral vectors should have high cellular uptake, excellent endosomal escape, and the ability to rapidly release the gene into the cytoplasm. Here, we developed a disulfide bond-conjugated bioreducible LMWSC-g-bPEI (LCP) composed of low molecular-weight water soluble chitosan (LMWSC), bPEI, and cystamine (Cys). The developed LCP had advantages such as low toxicity, great endosomal escape, and rapid release of pDNA into the cytoplasm. The polyplexes with LCP showed higher uptake into the nucleus and greater transfection efficiency than that without disulfide bond...
December 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29046393/-rac1-stimulated-macropinocytosis-enhances-g%C3%AE-%C3%AF-activation-of-pi3k%C3%AE
#18
Zahra Erami, Bassem D Khalil, Gilbert Salloum, Yanhua Yao, Jaclyn LoPiccolo, Aliaksei Shymanets, Bernd Nürnberg, Anne R Bresnick, Jonathan M Backer
Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of upstream activators, including receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families. For the Class IA PI 3-kinase PI3Kβ, two mechanisms for GPCR-mediated regulation have been described: direct binding of Gβγ subunits to the C2-helical domain linker of p110β, and Dock180/Elmo1-mediated activation of Rac1, which binds to the Ras-Binding Domain of p110β. We now show that the integration of these dual pathways is unexpectedly complex...
October 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29040339/protein-tyrosine-phosphatase-ptpn22-is-dispensable-for-dendritic-cell-antigen-processing-and-promotion-of-t-cell-activation-by-dendritic-cells
#19
Fiona Clarke, Christine K Jordan, Enrique Gutiérrez-Martinez, Jack A Bibby, Cristina Sanchez-Blanco, Georgina H Cornish, Xuezhi Dai, David J Rawlings, Rose Zamoyska, Pierre Guermonprez, Andrew P Cope, Harriet A Purvis
The PTPN22R620W single nucleotide polymorphism increases the risk of developing multiple autoimmune diseases including type 1 diabetes, rheumatoid arthritis and lupus. PTPN22 is highly expressed in antigen presenting cells (APCs) where the expression of the murine disease associated variant orthologue (Ptpn22R619W) is reported to dysregulate pattern recognition receptor signalling in dendritic cells (DCs) and promote T-cell proliferation. Because T-cell activation is dependent on DC antigen uptake, degradation and presentation, we analysed the efficiency of these functions in splenic and GM-CSF bone marrow derived DC from wild type (WT), Ptpn22-/- or Ptpn22R619W mutant mice...
2017: PloS One
https://www.readbyqxmd.com/read/29032193/selenium-functionalized-liposomes-for-systemic-delivery-of-doxorubicin-with-enhanced-pharmacokinetics-and-anticancer-effect
#20
Qian Xie, Wenji Deng, Xue Yuan, Huan Wang, Zhiguo Ma, Baojian Wu, Xingwang Zhang
Liposomes have shown to be an excellent drug delivery system, but the short in vivo fate discourages their popularity. This work aimed to develop selenium-functionalized liposomes (SeLPs) for doxorubicin (Dox) delivery to prolong the systemic circulation of liposomes by in situ selenium coating and enhance the anticancer effect via the synergy between Dox and selenium. Dox-loaded SeLPs (Dox-SeLPs) were prepared by film hydration/active loading/in situ reduction technique and characterized by particle size, entrapment efficiency and morphology...
October 12, 2017: European Journal of Pharmaceutics and Biopharmaceutics
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