scholarly journals RLIP76 (RalBP1) is an R-Ras effector that mediates adhesion-dependent Rac activation and cell migration

2006 ◽  
Vol 174 (6) ◽  
pp. 877-888 ◽  
Author(s):  
Lawrence E. Goldfinger ◽  
Celeste Ptak ◽  
Erin D. Jeffery ◽  
Jeffrey Shabanowitz ◽  
Donald F. Hunt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Malignant Transformation ◽  
Cell Spreading ◽  
Small Gtpases ◽  
Dependent Manner ◽  
Interacting Proteins ◽  
Ras Family ◽  
Ras Effectors ◽  
And Migration

The Ras family of small GTPases regulates cell proliferation, spreading, migration and apoptosis, and malignant transformation by binding to several protein effectors. One such GTPase, R-Ras, plays distinct roles in each of these processes, but to date, identified R-Ras effectors were shared with other Ras family members (e.g., H-Ras). We utilized a new database of Ras-interacting proteins to identify RLIP76 (RalBP1) as a novel R-Ras effector. RLIP76 binds directly to R-Ras in a GTP-dependent manner, but does not physically associate with the closely related paralogues H-Ras and Rap1A. RLIP76 is required for adhesion-induced Rac activation and the resulting cell spreading and migration, as well as for the ability of R-Ras to enhance these functions. RLIP76 regulates Rac activity through the adhesion-induced activation of Arf6 GTPase and activation of Arf6 bypasses the requirement for RLIP76 in Rac activation and cell spreading. Thus, we identify a novel R-Ras effector, RLIP76, which links R-Ras to adhesion-induced Rac activation through a GTPase cascade that mediates cell spreading and migration.

scholarly journals Metformin Suppressed CXCL8 Expression and Cell Migration in HEK293/TLR4 Cell Line

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhihui Xiao ◽  
Wenjun Wu ◽  
Vladimir Poltoratsky
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Tumor Cell ◽  
Nuclear Translocation ◽  
High Dose ◽  
Dependent Manner ◽  
Tumor Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Chronic inflammation is associated with cancer. CXCL8 promotes tumor microenvironment construction through recruiting leukocytes and endothelial progenitor cells that are involved in angiogenesis. It also enhances tumor cell proliferation and migration. Metformin, type II diabetes medication, demonstrates anticancer properties via suppressing inflammation, tumor cell proliferation, angiogenesis, and metastasis. This study intended to address the role of metformin in regulation of CXCL8 expression and cell proliferation and migration. Our data indicated that metformin suppressed LPS-induced CXCL8 expression in a dose-dependent manner through inhibiting NF-κB, but not AP-1 and C/EBP, activities under the conditions we used. This inhibitory effect of metformin is achieved through dampening LPS-induced NF-κB nuclear translocation. Cell migration was inhibited by metformin under high dose (10 mM), but not cell proliferation.

scholarly journals MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Zhenzhao Luo ◽  
Yue Fan ◽  
Xianchang Liu ◽  
Shuiyi Liu ◽  
Xiaoyu Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Growth ◽  
Suppressive Effect ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Suppress Cell Proliferation

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3′UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

Cell proliferation and migration on collagen substrata in vitro

1980 ◽  
Vol 41 (1) ◽  
pp. 159-175
Author(s):  
S.L. Schor
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Collagen Gel ◽  
Collagen Fibres ◽  
3 Dimensional ◽  
Cell Proliferation And Migration ◽  
Native Collagen ◽  
And Migration ◽  
Collagen Gel Matrix ◽  
Proliferation And Migration

Quantitative data are presented regarding cell proliferation and migration on (a) collagen films (b) the surface of 3-dimensional gels of native collagen fibres and (c) within the 3-dimensional collagen gel matrix, as part of a study of the effects of the extracellular matrix on cell behaviour. The nature of the collagen environment was found to influence the proliferation of certain cell types, but not of others. For example, HeLa cells proliferate at approximately the same rate and reach the same saturation cell densities on all of the collagen substrata, while human skin fibroblasts grow more slowly within the 3-dimensional collagen gel matrix compared with cells either on the gel surface or on collagen films. The 3-dimensional gels of native collagen fibres may also be used to study cell migration on the gel surface, as well as cell migration (or ‘infiltration’) from the gel surface into the 3-dimensional collagen matrix. Two methods have been used to obtain quantitative information concerning cell infiltration into the collagen gel, one involving the selective removal of cells from the gel surface, while the other relies on direct microscopic examination. Of the cells examined to date, epithelial cells (both normal and tumour) do not show infiltrative behaviour, while both normal and virally transformed fibroblasts, as well as tumour cells of non-epithelial origin (e.g. melanoma), do infiltrate into the collagen gel matrix, at rates which vary considerably according to cell type.

Urokinase-induced migration of human vascular smooth muscle cells requires coupling of the small GTPases RhoA and Rac1 to the Tyk2/PI3-K signalling pathway

2003 ◽  
Vol 89 (05) ◽  
pp. 904-914 ◽  
Author(s):  
Natalia Tkachuk ◽  
Hermann Haller ◽  
Inna Dumler ◽  
Ioulia Kiian
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Vascular Smooth Muscle ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Small Gtpases ◽  
Janus Kinase ◽  
Immunocytochemical Staining ◽  
Boyden Chamber ◽  
Dependent Manner

SummaryUrokinase-type plasminogen activator (uPA) facilitates cell migration by localizing proteolisys on the cell surface and by inducing intracellular signalling pathways. In human vascular smooth muscle cell (VSMC) uPA stimulates migration via the uPA receptor (uPAR) signalling complex containing the Janus kinase Tyk2 and phosphatidylinositol 3-kinase (PI3-K). We report that active GTP-bound forms of small GTPases RhoA and Rac1, but not Cdc42, are directly associated with Tyk2 and PI3-K in an uPA/uPAR-dependent fashion. Endogenous RhoA, but not Rac1 or Cdc42, was significantly activated in response to uPA. RhoA activation was abolished by cell treatment with two unrelated, structurally distinct, specific inhibitors of PI3-K, wortmannin, and LY294002. Downstream of RhoA, phosphorylation of myosin light chain (MLC) was dramatically upregulated by uPA in a Rho kinase- and PI3-K-dependent manner. Thus, selective Rho kinase inhibitor Y27632 and PI3-K inhibitors wortmannin and LY294002 prevented the uPA-induced stimulation of MLC phosphorylation. Rho kinase inhibition also decreased uPA-stimulated VSMC migration as observed in a Boyden chamber. VSMC immunocytochemical staining demonstrated redistribution of RhoA and Rac1 active forms to the newly formed leading edge of migrating cell. VSMC microinjection with antibodies to either Rho or Rac1 decreased uPA-stimulated cell migration, indicating the involvement of both GTPases in the migration process. Our results provide evidence that the small GTPases RhoA and Rac1, together with Rho kinase, are necessary to mediate the uPA/uPAR-directed migration via the Tyk2/PI3-K signalling complex in human VSMC.

scholarly journals The inositol 5-phosphatase SHIP2 is an effector of RhoA and is involved in cell polarity and migration

2012 ◽  
Vol 23 (13) ◽  
pp. 2593-2604 ◽  
Author(s):  
Katsuhiro Kato ◽  
Tsubasa Yazawa ◽  
Kentaro Taki ◽  
Kazutaka Mori ◽  
Shujie Wang ◽  
...  
Keyword(s):  
Small Gtpases ◽  
Cell Polarization ◽  
Dependent Manner ◽  
Wild Type ◽  
Functional Interaction ◽  
Src Homology 2 ◽  
Motile Cells ◽  
Lipid Turnover ◽  
Src Homology ◽  
And Migration

Cell migration is essential for various physiological and pathological processes. Polarization in motile cells requires the coordination of several key signaling molecules, including RhoA small GTPases and phosphoinositides. Although RhoA participates in a front–rear polarization in migrating cells, little is known about the functional interaction between RhoA and lipid turnover. We find here that src-homology 2–containing inositol-5-phosphatase 2 (SHIP2) interacts with RhoA in a GTP-dependent manner. The association between SHIP2 and RhoA is observed in spreading and migrating U251 glioma cells. The depletion of SHIP2 attenuates cell polarization and migration, which is rescued by wild-type SHIP2 but not by a mutant defective in RhoA binding. In addition, the depletion of SHIP2 impairs the proper localization of phosphatidylinositol 3,4,5-trisphosphate, which is not restored by a mutant defective in RhoA binding. These results suggest that RhoA associates with SHIP2 to regulate cell polarization and migration.

Abstract 451: Oxygen Regulation of Human Coronary Artery Smooth Muscle Cell Proliferation and Migration

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Mingming Yang ◽  
Tomoko Kamishima ◽  
Caroline Dart ◽  
John M Quayle
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Coronary Artery ◽  
Cell Viability ◽  
Smooth Muscle Cell ◽  
Human Coronary Artery ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Introduction: Intimal thickening of blood vessels, a hallmark of several vascular diseases including atherosclerosis and a potential point of therapeutic intervention, is caused by vascular smooth muscle cell proliferation and migration. It has been suggested that oxygen availability in vessels not only regulates behavior of smooth muscle cells but also serves as a trigger that may lead to pathological responses. In this study we determined whether hypoxia elicits proliferative and migratory responses in Human Coronary Artery SMCs (HCASMCs). Methods: Proliferation of HCASMCs was assessed using a 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. SMCs were plated in 96-well plates (n=5), serum starved, and then placed under hypoxic or normoxic conditions for 2, 4 and 6 days (2D/4D/6D) before MTT was added to each well. Absorbance at the wavelength 570 nm was read on an ELISA plate reader, and percent change in cell viability was determined and normalized to control (cell viability under normoxia). Cell migration was characterized by scratch-wound assay. SMCs were seeded in 6 well plates overnight (n=3), then a ‘scratch’ on the cell monolayer was created for each well before putting into different oxygen levels for 4 hours, 12 hours and 24 hours. Images were captured at the beginning and at intervals during cell migration to close the scratch, and the degree of migration was determined by comparing the images. Results: Compared to normoxic condition, cell number changed to 118.1%±1.3% in 5% O 2 (p<0.05) and 98.2%%±1.9% in 1% O 2 after 2D; to 151.9% ±8.5% in 5% O 2 (p<0.001) and 119.4%±5.0% in 1% O 2 (p<0.05) after 4D; and to 163.0%±4.3% in 5% O 2 (p<0.001) and 120.3%±2.2% in 1% O 2 (p<0.05) after 6D. In the cell migration assay, the difference in migration rate between different groups after 4 hours was not obvious, but there was a significant difference after 12 hours (29.3%±1.3% closure in normoxia vs 39.8%±1.9% in 5% O 2 vs 40.9%±3.5% in 1% O 2 , p<0.05) and 24 hours (71.5%±4.4% in normoxia vs 87.2%±2.2% in 5% O 2 vs 87.5%±3.1% in 1% O 2 , p<0.05). Conclusion: Our studies reveal that hypoxia induces both proliferation and migration of HCASMCs.

Regulation of cell migration by the integrin beta subunit ectodomain

1996 ◽  
Vol 109 (6) ◽  
pp. 1615-1622 ◽  
Author(s):  
E.J. Filardo ◽  
S.L. Deming ◽  
D.A. Cheresh
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Cell Spreading ◽  
Biological Properties ◽  
Beta Subunit ◽  
Integrin Subunit ◽  
Cytokine Activation ◽  
Factor Alpha ◽  
And Migration ◽  
Alpha V Beta 3

CS-1 melanoma cells transfected with cDNAs encoding either the beta 3 or beta 5 integrin subunit protein express alpha v beta 3 or alpha v beta 5, respectively, enabling them to adhere to vitronectin yet only alpha v beta 3 promotes cell spreading and migration on this substrate. Following exposure to insulin or insulin-like growth factor, alpha v beta 5-expressing CS-1 cells gain the ability to migrate on vitronectin. To identify structural regions in beta 3 or beta 5 that account for these distinct biological properties, CS-1 cells were transfected with one of two chimeric beta subunit proteins, in which the ecto- and cytoplasmic domains of beta 3 and beta 5 were exchanged (termed alpha v beta 3/5 or alpha v beta 5/3). Surprisingly, alpha v beta 3/5 expressing cells spread and migrate on vitronectin while cells expressing alpha v beta 5/3 do not unless they are exposed to cytokine. These findings suggest that the distinct migratory properties mediated by integrins alpha v beta 3 and alpha v beta 5 and their response to cytokine activation is determined by a sequence(s) within the ectodomain of the integrin beta subunit.

The Dictyostelium RasS protein is required for macropinocytosis, phagocytosis and the control of cell movement

2000 ◽  
Vol 113 (4) ◽  
pp. 709-719 ◽  
Author(s):  
J.R. Chubb ◽  
A. Wilkins ◽  
G.M. Thomas ◽  
R.H. Insall
Keyword(s):  
Cell Migration ◽  
Significant Proportion ◽  
Cell Movement ◽  
Fluid Phase ◽  
Small Gtpases ◽  
Cell Cortex ◽  
Fluid Phase Endocytosis ◽  
Ras Family ◽  
Actin Protrusions ◽  
Mutant Cells

Endocytosis and cell migration both require transient localised remodelling of the cell cortex. Several lines of evidence suggest a key regulatory role in these activities for members of the Ras family of small GTPases. We have generated Dictyostelium cells lacking one member of this family, RasS, and the mutant cells are perturbed in endocytosis and cell migration. Mutant amoebae are defective in phagocytosis and fluid-phase endocytosis and are impaired in growth. Conversely, the rasS(-)cells show an enhanced rate of cell migration, moving three times faster than wild-type controls. The mutant cells display an aberrant morphology, are highly polarised, carry many elongated actin protrusions and show a concomitant decrease in formation of pinocytic crowns on the cell surface. These morphological aberrations are paralleled by changes in the actin cytoskeleton, with a significant proportion of the cortical F-actin relocalised to prominent pseudopodia. Rapid migration and endocytosis appear to be mutually incompatible and it is likely that RasS protein is required to maintain the normal balance between these two actin-dependent processes.

scholarly journals The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia

2018 ◽  
Vol 47 (3) ◽  
pp. 981-993 ◽  
Author(s):  
Yu Chen ◽  
Tongtong Wang ◽  
Jing Du ◽  
Yanchun Li ◽  
Xin Wang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Proliferation And Apoptosis ◽  
And Migration

Background/Aims: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line. Methods: Firstly, K562 cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry with Annexin V-FITC/PI staining. Cell migration was measured by Transwell migration assay. In addition, western blot was performed to determine the proteins (PI3K, Bax, Bcl-2, cleaved caspase-3, PTEN, p-AKT, AKT, CXCR4, SDF-1, CD44) involved in the mechanism of action of shikonin. Finally, neutrophils from peripheral blood of CML patients were obtained, and cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry. Results: Shikonin reduced the proliferation of K562 cells in a time- and dose-dependent manner and promoted the apoptosis of K562 cells. Moreover, shikonin increased the PTEN level and inactivated the PI3K/AKT signaling pathway, subsequently upregulating BAX in K562 cells. In addition, shikonin could block K562 cell migration via the CXCR4/SDF-1 axis. Finally, shikonin significantly inhibited the proliferation and promoted the apoptosis of neutrophils from CML patients. Conclusion: These results demonstrated that shikonin inhibits CML proliferation and migration and induces apoptosis by the PTEN/PI3K/AKT pathway, revealing the effects of shikonin therapy on CML.

scholarly journals Lobaplatin Inhibits Prostate Cancer Proliferation and Migration Through Regulation of BCL2 and BAX

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581985098 ◽  
Author(s):  
Hongwen Cao ◽  
Yigeng Feng ◽  
Lei Chen ◽  
Chao Yu
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Cancer Proliferation ◽  
Expression Levels ◽  
And Migration ◽  
Proliferation And Migration

Lobaplatin is a diastereometric mixture of platinum (II) complexes, which contain a 1,2-bis (aminomethyl) cyclobutane stable ligand and lactic acid. Previous studies have showed that lobaplatin plays inhibiting roles in various types of tumors. However, the role of lobaplatin in prostate cancer remains unknown. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell proliferation was detected by cell colony formation assay. Cell migration and invasion were determined by transwell migration and invasion assay. Cell apoptosis was detected by flow cytometry. The messenger RNA and protein expression levels were detected by quantitative real-time polymerase chain reaction and Western blot. Lobaplatin treatment inhibits cell viability, cell proliferation, cell migration, and invasion, while promotes cell apoptosis of prostate cancer cell lines DU145 and PC3. Meanwhile, lobaplatin treatment regulates apoptosis by downregulation of BCL2 expression and upregulation of BAX expression levels. Our study suggests lobaplatin inhibits prostate cancer proliferation and migration through regulation of BCL2 and BAX expression.

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