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https://www.readbyqxmd.com/read/29667279/baicalein-disturbs-the-morphological-plasticity-and-motility-of-breast-adenocarcinoma-cells-depending-on-the-tumor-microenvironment
#1
Takeshi Terabayashi, Katsuhiro Hanada, Kou Motani, Hidetaka Kosako, Mami Yamaoka, Toshihide Kimura, Toshimasa Ishizaki
During tumor invasion, cancer cells change their morphology and mode of migration based on communication with the surrounding environment. Numerous studies have indicated that paracrine interactions from non-neoplastic cells impact the migratory and invasive properties of cancer cells. Thus, these interactions are potential targets for anticancer therapies. In this study, we showed that the flavones member baicalein suppresses the motility of breast cancer cells that is promoted by paracrine interactions. First, we identified laminin-332 (LN-332) as a principle paracrine factor in conditioned medium from mammary epithelium-derived MCF10A cells that regulates the morphology and motility of breast adenocarcinoma MDA-MB-231 cells...
April 18, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29666462/tranilast-inhibits-the-expression-of-genes-related-to-epithelial-mesenchymal-transition-and-angiogenesis-in-neurofibromin-deficient-cells
#2
Ritsuko Harigai, Shigeki Sakai, Hiroyuki Nobusue, Chikako Hirose, Oltea Sampetrean, Noriaki Minami, Yukie Hata, Takashi Kasama, Takanori Hirose, Toshiki Takenouchi, Kenjiro Kosaki, Kazuo Kishi, Hideyuki Saya, Yoshimi Arima
Neurofibromatosis type 1 (NF1) is caused by germline mutations in the NF1 gene and is characterized by café au lait spots and benign tumours known as neurofibromas. NF1 encodes the tumour suppressor protein neurofibromin, which negatively regulates the small GTPase Ras, with the constitutive activation of Ras signalling resulting from NF1 mutations being thought to underlie neurofibroma development. We previously showed that knockdown of neurofibromin triggers epithelial-mesenchymal transition (EMT) signalling and that such signalling is activated in NF1-associated neurofibromas...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29663616/ehrho1-regulates-phagocytosis-by-modulating-actin-dynamics-through-ehformin1-and-ehprofilin1-in-entamoeba-histolytica
#3
Ravi Bharadwaj, Shalini Sharma, Janhawi, Ranjana Arya, Sudha Bhattacharya, Alok Bhattacharya
The protist parasite Entamoeba histolytica causes amoebiasis, a major public health problem in developing countries and a major cause of morbidity and mortality. Invasive infection in amoebiasis mostly affects intestinal epithelial cell lining, but can also involve other organs, such as liver, lungs or brain. Phagocytosis is an essential mode of nutrition in amoeba and has often been associated with virulence behaviour of E. histolytica. E. histolytica possesses a highly dynamic and actin-rich cytoskeleton that is thought to be involved in many processes, such as motility, pseudopod formation and pathogenesis...
April 17, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29663589/tying-trafficking-to-fusion-and-fission-at-the-mighty-mitochondria
#4
REVIEW
Trey Farmer, Naava Naslavsky, Steve Caplan
The mitochondrion is a unique organelle that serves as the main site of adenosine triphosphate (ATP) generation needed for energy in the cell. However, mitochondria also play essential roles in cell death through apoptosis and necrosis, as well as a variety of crucial functions related to stress regulation, autophagy, lipid synthesis, and calcium storage. There is a growing appreciation that mitochondrial function is regulated by the dynamics of its membrane fusion and fission; longer, fused mitochondria are optimal for ATP generation, whereas fission of mitochondria facilitates mitophagy and cell division...
April 16, 2018: Traffic
https://www.readbyqxmd.com/read/29662661/targeting-oncogenic-ras-by-the-clostridium-perfringens-toxin-tpel
#5
Björn Schorch, Hannah Heni, Nour-Imene Zahaf, Tilman Brummer, Marina Mione, Gudula Schmidt, Panagiotis Papatheodorou, Klaus Aktories
Clostridium perfringens toxin TpeL belongs to the family of large clostridial glycosylating toxins. The toxin causes N-acetylglucosaminylation of Ras proteins at threonine35 thereby inactivating the small GTPases. Here, we show that all main types of oncogenic Ras proteins (H-Ras, K-Ras and N-Ras) are modified by the toxin in vitro and in vivo . Toxin-catalyzed modification of Ras was accompanied by inhibition of the MAP kinase pathway. Importantly, TpeL inhibited the paradoxical activation of the MAP kinase pathway induced by the BRAF inhibitor Vemurafenib in the human melanoma cell line SBCL2...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29661855/the-heptad-repeat-domain-1-of-mitofusin-has-membrane-destabilization-function-in-mitochondrial-fusion
#6
Frédéric Daste, Cécile Sauvanet, Andrej Bavdek, James Baye, Fabienne Pierre, Rémi Le Borgne, Claudine David, Manuel Rojo, Patrick Fuchs, David Tareste
Mitochondria are double-membrane-bound organelles that constantly change shape through membrane fusion and fission. Outer mitochondrial membrane fusion is controlled by Mitofusin, whose molecular architecture consists of an N-terminal GTPase domain, a first heptad repeat domain (HR1), two transmembrane domains, and a second heptad repeat domain (HR2). The mode of action of Mitofusin and the specific roles played by each of these functional domains in mitochondrial fusion are not fully understood. Here, using a combination of in situ and in vitro fusion assays, we show that HR1 induces membrane fusion and possesses a conserved amphipathic helix that folds upon interaction with the lipid bilayer surface...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29661000/regulation-of-clathrin-mediated-endocytosis
#7
Marcel Mettlen, Ping-Hung Chen, Saipraveen Srinivasan, Gaudenz Danuser, Sandra L Schmid
Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian cells. It is responsible for the uptake of transmembrane receptors and transporters, for remodeling plasma membrane composition in response to environmental changes, and for regulating cell surface signaling. CME occurs via the assembly and maturation of clathrin-coated pits that concentrate cargo as they invaginate and pinch off to form clathrin-coated vesicles. In addition to the major coat proteins, clathrin triskelia and adaptor protein complexes, CME requires a myriad of endocytic accessory proteins and phosphatidylinositol lipids...
April 16, 2018: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/29659741/formin-2-regulates-lysosomal-degradation-of-wnt-associated-%C3%AE-catenin-in-neural-progenitors
#8
Gewei Lian, Anjen Chenn, Victor Ekuta, Sneha Kanaujia, Volney Sheen
Although neural progenitor proliferation along the ventricular zone is regulated by β-catenin through Wnt signaling, the cytoskeletal mechanisms that regulate expression and localization of these proteins are not well understood. Our prior studies have shown that loss of the actin-binding Filamin A (FlnA) and actin-nucleating protein Formin 2 (Fmn2) impairs endocytosis of low-density-lipoprotein-receptor-related protein 6 (Lrp6), thereby disrupting β-catenin activation, resulting in decreased brain size. Here, we report that activated RhoA-GTPase disengages Fmn2 N- to C-terminal binding to promote Fmn2 activation and redistribution into lysosomal vesicles...
April 5, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29657248/association-of-fat-mass-and-obesity-associated-and-retinitis-pigmentosa-guanosine-triphosphatase-gtpase-regulator-interacting-protein-1-like-polymorphisms-with-body-mass-index-in-chinese-women
#9
Boyu Chen, Zhiqiang Li, Jianhua Chen, Jue Ji, Jingyi Shen, Yufeng Xu, Yingying Zhao, Danping Liu, Yinhuan Shen, Weijie Zhang, Jiawei Shen, Yonggang Wang, Yongyong Shi
Body mass index (BMI) is the most commonly used quantitative measure of adiposity. It is a kind of complex genetic diseases which are caused by multiple susceptibility genes. The first intron of fat mass and obesity-associated (FTO) has been widely discovered to be associated with BMI. Retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) is located in the upstream region of FTO and has been proved to be linked with obesity through functional tests. We carried out a genetic association analysis to figure out the role of the FTO gene and the RPGRIP1L gene in BMI...
April 14, 2018: Endocrine Journal
https://www.readbyqxmd.com/read/29656322/p190rhogap-prevents-mitotic-spindle-fragmentation-and-is-required-to-activate-aurora-a-kinase-at-acentriolar-poles
#10
Arkadi Manukyan, Lilit Sargsyan, Sarah J Parsons, P Todd Stukenberg
Assembly of the mitotic spindle is essential for proper chromosome segregation during mitosis. Maintenance of spindle poles requires precise regulation of kinesin- and dynein-generated forces, and improper regulation of these forces disrupts pole integrity leading to pole fragmentation. The formation and function of the mitotic spindle are regulated by many proteins, including Aurora A kinase and the motor proteins Kif2a and Eg5. Here, we characterize a surprising role for the RhoA GTPase-activating protein, p190RhoGAP, in regulating the mitotic spindle...
April 14, 2018: Chromosoma
https://www.readbyqxmd.com/read/29653269/microrna-26a-is-a-key-regulon-that-inhibits-progression-and-metastasis-of-c-myc-ezh2-double-high-advanced-hepatocellular-carcinoma
#11
Xiang Zhang, Xiao Zhang, Ting Wang, Lei Wang, Zhijun Tan, Wei Wei, Bo Yan, Jing Zhao, Kaichun Wu, Angang Yang, Rui Zhang, Lintao Jia
Overexpressed c-Myc and EZH2 usually mean high malignancy in cancers. Most of mortality from cancer is attributable to metastasis. MicroRNAs(miRNAs), like transcription factors, can regulate hundreds of genes. Here, we identify microRNA-26a (miR-26a) suppresses EZH2 and c-Myc by targeting EZH2 and CDK8 in Wnt pathway. MiR-26a is a well-known tumor-suppressive miRNA in multiple cancers, but how it is downregulated in hepatocellular carcinoma (HCC) is still unclear. Here, we disclose miR-26a is epigenetic silenced by a c-Myc-mediated PRC2-depandent way in HCC...
April 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29652933/rhogapp190-a-potential-player-in-tbph-mediated-neurodegeneration-in-drosophila
#12
Simona Langellotti, Giulia Romano, Fabian Feiguin, Francisco Ernesto Baralle, Maurizio Romano
TDP-43 is an ubiquitous and highly conserved ribonucleoprotein involved in several cellular processes including pre-mRNA splicing, transcription, mRNA stability and transport. Notwithstanding the evidence of TDP-43 involvement in the pathogenesis of different neurodegenerative disorders (i.e. ALS and FTLD), the underlying mechanisms are still unclear. Given the high degree of functional similarity between the human and fly orthologs of TDP-43, Drosophila melanogaster is a simple and useful model to study the pathophysiological role of this protein in vivo...
2018: PloS One
https://www.readbyqxmd.com/read/29652865/calsenilin-a-presenilin-interactor-regulates-rhoa-signaling-and-neurite-outgrowth
#13
Hee-Jun Kim, Won-Haeng Lee, Mo-Jong Kim, Sunmee Shin, Byungki Jang, Jae-Bong Park, Wilma Wasco, Joseph D Buxbaum, Yong-Sun Kim, Eun-Kyoung Choi
Calsenilin modulates A-type potassium channels, regulates presenilin-mediated γ-secretase activity, and represses prodynorphin and c-fos genes expression. RhoA is involved in various cellular functions including proliferation, differentiation, migration, transcription, and regulation of the actin cytoskeleton. Although recent studies demonstrate that calsenilin can directly interact with RhoA and that RhoA inactivation is essential for neuritogenesis, it is uncertain whether there is a link between calsenilin and RhoA-regulated neuritogenesis...
April 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29651441/stat1-igf1-rac1-and-mdm2-are-associated-with-recurrence-of-giant-cell-tumor-of-bone
#14
Shuxin Chen, Zepeng Du, Bingli Wu, Huiyang Shen, Chunpeng Liu, Xueli Qiu, Yufeng Zhang, Liyan Xu, Enmin Li, Zhigang Zhong
Background: In our previous study, mouse double minute 2 homolog (MDM2), insulin-like growth factor 1 (IGF1), signal transducer and activator of transcription 1 (STAT1), and Rac family small GTPase 1 (RAC1) were correlated with the recurrence of giant cell tumor of bone (GCT). The aim of this study is to use a large cohort study to confirm the involvement of these four genes in GCT recurrence. Methods: The expression of these four genes was detected and compared between GCT patients with or without recurrence...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29649639/cobalt-ii-ions-and-nanoparticles-induce-macrophage-retention-by-ros-mediated-down-regulation-of-rhoa-expression
#15
Jing Xu, Junyao Yang, Agata Nyga, Mazdak Ehteramyan, Ana Moraga, Yuanhao Wu, Lingfang Zeng, Martin M Knight, Julia C Shelton
Histological assessments of synovial tissues from patients with failed CoCr alloy hip prostheses demonstrate extensive infiltration and accumulation of macrophages, often loaded with large quantities of particulate debris. The resulting adverse reaction to metal debris (ARMD) frequently leads to early joint revision. Inflammatory response starts with the recruitment of immune cells and requires the egress of macrophages from the inflamed site for resolution of the reaction. Metal ions (Co2+ and Cr3+ ) have been shown to stimulate the migration of T lymphocytes but their effects on macrophages motility are still poorly understood...
April 9, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29649212/principles-that-govern-competition-or-co-existence-in-rho-gtpase-driven-polarization
#16
Jian-Geng Chiou, Samuel A Ramirez, Timothy C Elston, Thomas P Witelski, David G Schaeffer, Daniel J Lew
Rho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for unipolar or multipolar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by two-component reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry...
April 12, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29648608/rab39a-a-rab-small-gtpase-with-a-prominent-role-in-cancer-stemness
#17
Tokuhiro Chano, Sofia Avnet
RAB39A is a Rab small GTPase that localizes at distinct subcellular compartments and regulates intracellular membrane trafficking pathways in vertebrate cells. RAB39A interacts with various molecules and modulates vesicular trafficking that regulates multiple biological pathways such as neuronal differentiation and/or autophagy. Among these pathways are Hippo and Notch signalings, microtubular organization, and mitophagy/autophagy. Although RAB39A has never been studied in cancer biology, it has been recently shown to promote cancer stemness and tumorigenesis...
April 10, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/29642957/characterization-of-mitochondrion-targeted-gtpases-in-plasmodium-falciparum
#18
Kirti Gupta, Ankit Gupta, Afreen Haider, Saman Habib
Ribosome assembly is critical for translation and regulating the response to cellular events and requires a complex interplay of ribosomal RNA and proteins with assembly factors. We investigated putative participants in the biogenesis of the reduced organellar ribosomes of Plasmodium falciparum and identified homologues of two assembly GTPases - EngA and Obg that were found in mitochondria. Both are indispensable in bacteria and P. berghei EngA is among the 'essential' parasite blood stage proteins identified recently...
April 12, 2018: Parasitology
https://www.readbyqxmd.com/read/29642594/allosteric-activation-of-gdp-bound-ras-isoforms-by-bisphenol-derivative-plasticisers
#19
Miriam Schöpel, Oleksandr Shkura, Jana Seidel, Klaus Kock, Xueyin Zhong, Stefanie Löffek, Iris Helfrich, Hagen S Bachmann, Jürgen Scherkenbeck, Christian Herrmann, Raphael Stoll
The protein family of small GTPases controls cellular processes by acting as a binary switch between an active and an inactive state. The most prominent family members are H-Ras, N-Ras, and K-Ras isoforms, which are highly related and frequently mutated in cancer. Bisphenols are widespread in modern life because of their industrial application as plasticisers. Bisphenol A (BPA) is the best-known member and has gained significant scientific as well as public attention as an endocrine disrupting chemical, a fact that eventually led to its replacement...
April 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29628140/disease-causing-mutations-in-the-g-protein-g%C3%AE-s-subvert-the-roles-of-gdp-and-gtp
#20
Qi Hu, Kevan M Shokat
The single most frequent cancer-causing mutation across all heterotrimeric G proteins is R201C in Gαs. The current model explaining the gain-of-function activity of the R201 mutations is through the loss of GTPase activity and resulting inability to switch off to the GDP state. Here, we find that the R201C mutation can bypass the need for GTP binding by directly activating GDP-bound Gαs through stabilization of an intramolecular hydrogen bond network. Having found that a gain-of-function mutation can convert GDP into an activator, we postulated that a reciprocal mutation might disrupt the normal role of GTP...
April 1, 2018: Cell
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