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https://www.readbyqxmd.com/read/29784011/extremely-low-frequency-electromagnetic-fields-promote-mesenchymal-stem-cell-migration-by-increasing-intracellular-ca-2-and-activating-the-fak-rho-gtpases-signaling-pathways-in-vitro
#1
Yingchi Zhang, Jiyuan Yan, Haoran Xu, Yong Yang, Wenkai Li, Hua Wu, Chaoxu Liu
BACKGROUND: The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. METHODS: We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs...
May 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29778569/mevalonate-pathway-blockage-enhances-the-efficacy-of-mtor-inhibitors-with-the-activation-of-retinoblastoma-protein-in-renal-cell-carcinoma
#2
Nobuhisa Hagiwara, Motoki Watanabe, Mahiro Iizuka-Ohashi, Isao Yokota, Seijiro Toriyama, Mamiko Sukeno, Mitsuhiro Tomosugi, Yoshihiro Sowa, Fumiya Hongo, Kazuya Mikami, Jintetsu Soh, Akira Fujito, Hiroaki Miyashita, Yukako Morioka, Tsuneharu Miki, Osamu Ukimura, Toshiyuki Sakai
Renal cell carcinoma (RCC) is the most common malignancy of kidney and remains largely intractable once it recurs after resection. mTOR inhibitors have been one of the mainstays used against recurrent RCC; however, there has been a major problem of the resistance to mTOR inhibitors, and thus new combination treatments with mTOR inhibitors are required. We here retrospectively showed that regular use of antilipidemic drug statins could provide a longer progression free survival (PFS) in RCC patients prescribed with an mTOR inhibitor everolimus than without statins (median PFS, 7...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#3
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29776664/rhod-localization-and-function-is-dependent-on-its-gtp-gdp-bound-state-and-unique-n-terminal-motif
#4
Magdalena Blom, Katarina Reis, Pontus Aspenström
The atypical Rho GTPase RhoD has previously been shown to have a major impact on the organization and function of the actin filament system. However, when first discovered, RhoD was found to regulate endosome trafficking and dynamics and we therefore sought to investigate this regulation in more detail. We found that exogenously expressed RhoD in human fibroblasts localized to vesicles and the plasma membrane and that the active GTP-bound conformation was required for the plasma membrane localization but not for vesicle localization...
May 16, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29773903/circadian-regulator-nr1d2-regulates-glioblastoma-cell-proliferation-and-motility
#5
Min Yu, Wenjing Li, Qianqian Wang, Yan Wang, Fei Lu
Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29772566/the-epigenetic-factor-kdm2b-regulates-emt-and-small-gtpases-in-colon-tumor-cells
#6
Nefeli Zacharopoulou, Anna Tsapara, Galatea Kallergi, Evi Schmid, Saad Alkahtani, Saud Alarifi, Philip N Tsichlis, Sotirios C Kampranis, Christos Stournaras
BACKGROUND/AIMS: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. METHODS: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins...
May 14, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29771639/hic-5-expression-is-a-major-indicator-of-cancer-cell-morphology-migration-and-plasticity-in-three-dimensional-matrices
#7
Anushree C Gulvady, Fatemeh Dubois, Nicholas O Deakin, Gregory J Goreczny, Christopher E Turner
The focal adhesion proteins, Hic-5 and Paxillin have been previously identified as key regulators of MDA-MB-231 breast cancer cell migration and morphologic mesenchymal-amoeboid plasticity in three-dimensional extracellular matrices. However, their respective roles in other cancer cell types has not been evaluated. Herein, utilizing 3D cell-derived matrices and fibronectin-coated 1D substrates, we show that across a variety of cancer cell lines, the level of Hic-5 expression serves as the major indicator of the cells primary morphology, plasticity and in vitro invasiveness...
May 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29768205/c-elegans-blastomeres-clear-the-corpse-of-the-second-polar-body-by-lc3-associated-phagocytosis
#8
Gholamreza Fazeli, Maurice Stetter, Jaime N Lisack, Ann M Wehman
To understand how undifferentiated pluripotent cells cope with cell corpses, we examined the clearance of polar bodies born during female meiosis. We found that polar bodies lose membrane integrity and expose phosphatidylserine in Caenorhabditis elegans. Polar body signaling recruits engulfment receptors to the plasma membrane of embryonic blastomeres using the PI3K VPS-34, RAB-5 GTPase and the sorting nexin SNX-6. The second polar body is then phagocytosed using receptor-mediated engulfment pathways dependent on the Rac1 ortholog CED-10 but undergoes non-apoptotic programmed cell death independent of engulfment...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29765517/targeting-the-mevalonate-pathway-is-a-novel-therapeutic-approach-to-inhibit-oncogenic-foxm1-transcription-factor-in-human-hepatocellular-carcinoma
#9
Satoshi Ogura, Yuichi Yoshida, Tomohide Kurahashi, Mayumi Egawa, Kunimaro Furuta, Shinichi Kiso, Yoshihiro Kamada, Hayato Hikita, Hidetoshi Eguchi, Hisakazu Ogita, Yuichiro Doki, Masaki Mori, Tomohide Tatsumi, Tetsuo Takehara
Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29762824/long-noncoding-rna-uca1-promotes-cell-proliferation-migration-and-invasion-of-human-leukemia-cells-via-sponging-mir-126
#10
M-D Sun, Y-Q Zheng, L-P Wang, H-T Zhao, S Yang
OBJECTIVE: Acute myeloid leukemia (AML) is a bone marrow malignancy. Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) plays an important role in several cancers. However, the role of lncRNA UCA1 in AML remained unclear. MATERIALS AND METHODS: LncRNA UCA1 expressions in different cell lines were determined by RT-PCR. In human myelogenous leukemia (ML) cell lines K562 and HL60, effects of lncRNA UCA1 knockdown on cell viability, migration, invasion, and apoptosis were assessed, respectively...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29753745/1-%C3%AE-25-dihydroxyvitamin-d-3-potentiates-avian-osteoclast-activation-by-increasing-the-formation-of-zipper-like-structure-via-src-rac1-signaling
#11
Dong Wang, Jian-Hong Gu, Ling-Ling Feng, Xi-Shuai Tong, Rui-Long Song, Hong-Yan Zhao, Jian-Chun Bian, Xue-Zhong Liu, Yan Yuan, Zong-Ping Liu
Avian bone metabolism diseases affect the development and production of chickens, and many of these diseases can be prevented and controlled by balanced nutrition and hormone medicine. The steroid hormone 1α,25-dihydroxyvitamin D3 plays a key role in maintaining the balance of avian bone metabolism. Clinically, 1α,25-(OH)2 D3 has been used to treat several bone diseases. Although several previous studies have investigated the effects of 1α,25-(OH)2 D3 on osteoclastogenesis, the mechanisms underpinning osteoclast (OC) activity remain largely unknown...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29752492/novel-antidepressant-effects-of-paeonol-alleviate-neuronal-injury-with-concomitant-alterations-in-bdnf-rac1-and-rhoa-levels-in-chronic-unpredictable-mild-stress-rats
#12
Xiu-Ling Zhu, Jing-Jing Chen, Fei Han, Chuan Pan, Ting-Ting Zhuang, Ya-Fei Cai, Ya-Ping Lu
RATIONALE: Increasing evidence has suggested that major depressive disorder (MDD) is highly associated with brain-derived neurotrophic factor (BDNF) levels, dendrites atrophy, and loss of dendritic spines, especially in emotion-associated brain regions including the hippocampus. Paeonol is a kind of polyphenols natural product with a variety of therapeutic effects. Recent studies have reported its antidepressant effects. However, it is unclear what signaling pathways contribute to improve MDD...
May 12, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29749029/rac1-muscle-knockout-exacerbates-the-detrimental-effect-of-high-fat-diet-on-insulin-stimulated-muscle-glucose-uptake-independently-of-akt
#13
Steffen H Raun, Mona Ali, Rasmus Kjøbsted, Lisbeth L V Møller, Morten A Federspiel, Erik A Richter, Thomas E Jensen, Lykke Sylow
KEY POINTS: The actin cytoskeleton regulating GTPase, Rac1, is a novel player in insulin-stimulated glucose uptake in muscle in vivo. High-fat diet (HFD) exacerbates muscle insulin resistance in Rac1 muscle knockout (mKO) mice. Muscle Rac1 KO protects against HFD-induced insulin resistance in fat tissue indicating tissue cross-talk. A fatty diet markedly reduces insulin clearance in mice. ABSTRACT: Insulin resistance and perturbations in glucose metabolism underpin common lifestyle diseases such as type 2 diabetes and obesity...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29745857/identification-of-novel-drug-targets-for-diamond-blackfan-anemia-based-on-rps19-gene-mutation-using-protein-protein-interaction-network
#14
Abbas Khan, Arif Ali, Muhammad Junaid, Chang Liu, Aman Chandra Kaushik, William C S Cho, Dong-Qing Wei
BACKGROUND: Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. In order to explore the molecular mechanisms of wild and mutated samples from DBA patients were exposed to bioinformatics investigation. Biological network of differentially expressed genes was constructed. This study aimed to identify novel therapeutic signatures in DBA and uncovered their mechanisms. The gene expression dataset of GSE14335 was used, which consists of 6 normal and 4 diseased cases...
April 24, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29740674/deacetylmycoepoxydiene-is-an-agonist-of-rac1-and-simultaneously-induces-autophagy-and-apoptosis
#15
Wei Xie, Wei Zhang, Mingwei Sun, Chunhua Lu, Yuemao Shen
Lung cancer is the second most common cause of cancer-related death in the world. Most cases of lung cancer are not curable, especially non-small cell lung cancer (NSCLC). Thus, novel treatment targets for this malignant disease are urgently needed. Here, we demonstrate the feasibility of Rac1 in treating p53-null human NSCLC H1299 as a novel drug target. Deacetylmycoepoxydiene (DA-MED), a cytotoxic natural polyketide, functions as a Rac1 agonist in p53-null NSCLC H1299 cells. DA-MED treatment drives Rac1 activation and promotes robust production of reactive oxygen species, activating mitochondrial permeability transition and the intrinsic apoptotic pathway...
May 9, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29740022/hyperactivity-of-rac1-gtpase-pathway-impairs-neuritogenesis-of-cortical-neurons-by-altering-actin-dynamics
#16
Valentina Zamboni, Maria Armentano, Gaia Berto, Elisa Ciraolo, Alessandra Ghigo, Donatella Garzotto, Alessandro Umbach, Ferdinando DiCunto, Elena Parmigiani, Marina Boido, Alessandro Vercelli, Nadia El-Assawy, Alessandro Mauro, Lorenzo Priano, Luisa Ponzoni, Luca Murru, Maria Passafaro, Emilio Hirsch, Giorgio R Merlo
The small-GTPase Rac1 is a key molecular regulator linking extracellular signals to actin cytoskeleton dynamics. Loss-of-function mutations in RAC1 and other genes of the Rac signaling pathway have been implicated in the pathogenesis of Intellectual Disability (ID). The Rac1 activity is negatively controlled by GAP proteins, however the effect of Rac1 hyperactivity on neuronal networking in vivo has been poorly studied. ArhGAP15 is a Rac-specific negative regulator, expressed in the main subtypes of pyramidal cortical neurons...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29734338/rit1-controls-actin-dynamics-via-complex-formation-with-rac1-cdc42-and-pak1
#17
Uta Meyer Zum Büschenfelde, Laura Isabel Brandenstein, Leonie von Elsner, Kristina Flato, Tess Holling, Martin Zenker, Georg Rosenberger, Kerstin Kutsche
RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1...
May 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29733372/cnf1-like-deamidase-domains-common-lego-bricks-among-cancer-promoting-immunomodulatory-bacterial-virulence-factors
#18
Mengfei Ho, Amel Mettouchi, Brenda A Wilson, Emmanuel Lemichez
Alterations of the cellular proteome over time due to spontaneous or toxin-mediated enzymatic deamidation of glutamine (Gln) and asparagine (Asn) residues contribute to bacterial infection and might represent a source of aging-related diseases. Here, we put into perspective what is known about the mode of action of the CNF1 toxin from pathogenic E. coli, a paradigm of bacterial deamidases that activate Rho GTPases, to illustrate the importance of determining whether exposure to these factors are risk factors in the etiology age-related diseases, such as cancer...
May 3, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29727463/chlamydia-exploits-filopodial-capture-and-a-macropinocytosis-like-pathway-for-host-cell-entry
#19
Charlotte Ford, Andrea Nans, Emmanuel Boucrot, Richard D Hayward
Pathogens hijack host endocytic pathways to force their own entry into eukaryotic target cells. Many bacteria either exploit receptor-mediated zippering or inject virulence proteins directly to trigger membrane reorganisation and cytoskeletal rearrangements. By contrast, extracellular C. trachomatis elementary bodies (EBs) apparently employ facets of both the zipper and trigger mechanisms and are only ~400 nm in diameter. Our cryo-electron tomography of C. trachomatis entry revealed an unexpectedly diverse array of host structures in association with invading EBs, suggesting internalisation may progress by multiple, potentially redundant routes or several sequential events within a single pathway...
May 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29726584/epithelial-mesenchymal-transition-softens-head-and-neck-cancer-cells-to-facilitate-migration-in-3d-environments
#20
Yin-Quan Chen, Hsin-Yi Lan, Yi-Chang Wu, Wen-Hao Yang, Arthur Chiou, Muh-Hwa Yang
The biological impact and signalling of epithelial-mesenchymal transition (EMT) during cancer metastasis has been established. However, the changes in biophysical properties of cancer cells undergoing EMT remain elusive. Here, we measured, via video particle tracking microrheology, the intracellular stiffness of head and neck cancer cell lines with distinct EMT phenotypes. We also examined cells migration and invasiveness in different extracellular matrix architectures and EMT-related signalling in these cell lines...
May 4, 2018: Journal of Cellular and Molecular Medicine
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