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Migration and lysosome

Jeffrey Zielich, Elena Tzima, Eva Ayla Schröder, Faten Jemel, Barbara Conradt, Eric J Lambie
P5B ATPases are present in the genomes of diverse unicellular and multicellular eukaryotes, indicating that they have an ancient origin, and that they are important for cellular fitness. Inactivation of ATP13A2, one of the four human P5B ATPases, leads to early-onset Parkinson's disease (Kufor-Rakeb Syndrome). The presence of an invariant PPALP motif within the putative substrate interaction pocket of transmembrane segment M4 suggests that all P5B ATPases might have similar transport specificity; however, the identity of the transport substrate(s) remains unknown...
2018: PloS One
Yumao Jiang, Yue Jiao, Yang Liu, Meiyu Zhang, Zhiguo Wang, Yujuan Li, Tao Li, Xiaoliang Zhao, Danqiao Wang
As shown in our previous study, sinomenine hydrochloride (SH), the major bioactive alkaloid isolated from Sinomenium acutum Rehd. et Wils. (Fam. Menispermaceae ), initiates the autophagy-mediated death of human glioblastoma cells by generating reactive oxygen species and activating the autophagy-lysosome pathway. However, its effects on the migration and invasion of human glioblastoma cells have not yet been elucidated. Therefore, human glioblastoma U87 and SF767 cells were treated with SH (0.125 and 0.25 mM) for 24 h, and cell migration and invasion were assessed using scratch wound healing, migration and invasion assays...
March 14, 2018: International Journal of Molecular Sciences
Yanbo Fan, Haocheng Lu, Wenying Liang, Minerva T Garcia-Barrio, Yanhong Guo, Ji Zhang, Tianqing Zhu, Yibai Hao, Jifeng Zhang, Y E Chen
<u>Rationale:</u> Post-ischemic angiogenesis is critical to limit the ischemic tissue damage and improve the blood flow recovery. The regulation and the underlying molecular mechanisms of post-ischemic angiogenesis are not fully unraveled. Transcription factor-EB (TFEB) is emerging as a master gene for autophagy and lysosome biogenesis. However, the role of TFEB in vascular disease is less understood. <u>Objective:</u> We aimed to determine the role of endothelial TFEB in post-ischemic angiogenesis and its underlying molecular mechanism...
February 21, 2018: Circulation Research
Sabrina Maisel, Derrick Broka, Joyce Schroeder
The Epidermal Growth Factor Receptor (EGFR) is frequently mutated and overexpressed in metastatic cancer. Although EGFR is a transmembrane tyrosine kinase localized to the basolateral membrane in normal epithelium, it is frequently found intracellularly localized in transformed cells. We have previously demonstrated the epithelial adaptor protein mucin 1 (MUC1) alters trafficking of EGFR, inhibiting its degradation and promoting its translocation to the nucleus, where it can directly modulate gene transcription...
January 19, 2018: Oncotarget
Genbao Shao, Ranran Wang, Aiqin Sun, Jing Wei, Ke Peng, Qian Dai, Wannian Yang, Qiong Lin
BACKGROUND: EGFR-dependent cell migration plays an important role in lung cancer progression. Our previous study observed that the HECT E3 ubiquitin ligase NEDD4 is significantly correlated with tumor metastasis and required for migration and invasion signaling of EGFR in gastric cancer cells. However, how NEDD4 promotes the EGFR-dependent lung cancer cell migration is unknown. This study is to elucidate the mechanism by which NEDD4 mediates the EGFR lung cancer migration signaling. METHODS: Lentiviral vector-loaded NEDD4 shRNA was used to deplete endogenous NEDD4 in lung cancer cell lines...
February 19, 2018: Molecular Cancer
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
2018: Cellular Physiology and Biochemistry
Zijian Liu, Xiang Fu, Wei Huang, Chunxia Li, Xinyan Wang, Bei Huang
Selenium-containing phycocyanin (Se-PC) has been proved to have many biological effects, including anti-inflammatory and antioxidant. In this study, we investigated the photodynamic therapy (PDT) effects of Se-PC against liver tumour in vitro and in vivo experiment. Our results demonstrated that the half lethal dose of Se-PC PDT on HepG2 cells was 100μg/ml PC containing 20% selenium. Se-PC location migration from lysosomes to mitochondria was time dependent. In in vivo experiments, the tumour inhibition rate was 75...
December 20, 2017: Journal of Photochemistry and Photobiology. B, Biology
Lu Wang, Yue Meng, Jian-Jun Xu, Qing-Yun Zhang
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a novel oncogene, whose overexpression is involved in cancer occurrence and progression. However, the mechanism of LAPTM4B transcriptional regulation remains unclear. In this study, the results of transcription factor (TF) profiling plate arrays indicated that AP4 was a potential transcription factor regulating LAPTM4B expression. LAPTM4B was positively correlated with AP4 and they were both associated with poor overall and disease-free survival...
January 29, 2018: Molecular Cancer Research: MCR
Hao Jiang, Qin Wang, Lin Li, Qin Zeng, Hanmei Li, Tao Gong, Zhirong Zhang, Xun Sun
Due to its safety and efficacy, aluminum hydroxide is used as an immune adjuvant in human vaccines for over 80 years. Being a Th2 stimulator, the classical gel-like adjuvant, however, fails to generate CD8+ T cell responses, which are important for cancer vaccines. Here, aluminum hydroxide is turned from gel into nano-sized vaccine carriers AlO(OH)-polymer nanoparticles (APNs) to promote their lymphatic migration. After actively uptaken via scavenger receptor-A by antigen-presenting cells (APCs) resident in lymph nodes (LNs), APNs destabilize lysosomes resulting in efficient cytosolic delivery and cross-presentation of antigens...
January 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Xing Zhang, Yichong Ning, Yuzhong Xiao, Huaxin Duan, Guifang Qu, Xin Liu, Yan Du, Dejian Jiang, Jianlin Zhou
The cancer-testis gene MAEL is involved in the development and progression of bladder, liver and colorectal cancers. However, its role in other cancers is unclear. By systematically analyzing transcriptomics and genomics data from various cancer databases, we identified that the MAEL gene is aberrantly elevated in gastric cancer (GC) tissues and that its expression is strongly negatively correlated with DNA methylation (Pearson's correlation coefficient = -0.675). Survival analysis revealed that MAEL expression may serve as a prognostic marker for GC patients (overall survival: hazard ratio [HR] = 1...
December 26, 2017: Oncotarget
Ximing Du, Armella Zadoorian, Ivan E Lukmantara, Yanfei Qi, Andrew J Brown, Hongyuan Yang
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large family of proteins that mainly function in lipid transport and sensing. ORP5 is an endoplasmic reticulum (ER)-anchored protein implicated in lipid transfer at the contact sites between the ER and other membranes. Recent studies indicate that ORP5 is also involved in cancer cell invasion and tumor progression. However, the molecular mechanism underlying ORP5's involvement in cancer is unclear. Here, we report that ORP5 promotes cell proliferation and motility of HeLa cells, an effect that depends on its functional OSBP-related domain (ORD)...
January 22, 2018: Journal of Biological Chemistry
Igor Kovačević, Tomohisa Sakaue, Jisca Majoleé, Manon C Pronk, Masashi Maekawa, Dirk Geerts, Mar Fernandez-Borja, Shigeki Higashiyama, Peter L Hordijk
RhoGTPases control endothelial cell (EC) migration, adhesion, and barrier formation. Whereas the relevance of RhoA for endothelial barrier function is widely accepted, the role of the RhoA homologue RhoB is poorly defined. RhoB and RhoA are 85% identical, but RhoB's subcellular localization and half-life are uniquely different. Here, we studied the role of ubiquitination for the function and stability of RhoB in primary human ECs. We show that the K63 polyubiquitination at lysine 162 and 181 of RhoB targets the protein to lysosomes...
January 22, 2018: Journal of Cell Biology
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
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
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
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
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
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
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
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
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