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Cortactin

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https://www.readbyqxmd.com/read/27911942/persistent-morbillivirus-infection-leads-to-altered-cortactin-distribution-in-histiocytic-sarcoma-cells-with-decreased-cellular-migration-capacity
#1
Vanessa Maria Pfankuche, Mohamed Sayed-Ahmed, Vanessa Bono Contioso, Ingo Spitzbarth, Karl Rohn, Reiner Ulrich, Ulrich Deschl, Arno Kalkuhl, Wolfgang Baumgärtner, Christina Puff
Histiocytic sarcomas represent rare but fatal neoplasms in humans. Based on the absence of a commercially available human histiocytic sarcoma cell line the frequently affected dog displays a suitable translational model. Canine distemper virus, closely related to measles virus, is a highly promising candidate for oncolytic virotherapy. Therapeutic failures in patients are mostly associated with tumour invasion and metastasis often induced by misdirected cytoskeletal protein activities. Thus, the impact of persistent canine distemper virus infection on the cytoskeletal protein cortactin, which is frequently overexpressed in human cancers with poor prognosis, was investigated in vitro in a canine histiocytic sarcoma cell line (DH82)...
2016: PloS One
https://www.readbyqxmd.com/read/27903975/cortactin-promotes-colorectal-cancer-cell-proliferation-by-activating-the-egfr-mapk-pathway
#2
Xiaojian Zhang, Kun Liu, Tao Zhang, Zhenlei Wang, Xuan Qin, Xiaoqian Jing, Haoxuan Wu, Xiaopin Ji, Yonggang He, Ren Zhao
Cortactin (CTTN) is overexpressed in various tumors, including head and neck squamous cell carcinoma and colorectal cancer (CRC), and can serve as a biomarker of cancer metastasis. We observed that CTTN promotes cancer cell proliferation in vitro and increases CRC tumor xenograft growth in vivo. CTTN expression increases EGFR protein levels and enhances the activation of the MAPK signaling pathway. CTTN expression also inhibits the ubiquitin-mediated degradation of EGFR by suppressing the coupling of c-Cbl with EGFR...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893827/astrocyte-structural-and-molecular-response-to-elevated-intraocular-pressure-occurs-rapidly-and-precedes-axonal-tubulin-rearrangement-within-the-optic-nerve-head-in-a-rat-model
#3
Shandiz Tehrani, Lauren Davis, William O Cepurna, Tiffany E Choe, Diana C Lozano, Ashley Monfared, Lauren Cooper, Joshua Cheng, Elaine C Johnson, John C Morrison
Glaucomatous axon injury occurs at the level of the optic nerve head (ONH) in response to uncontrolled intraocular pressure (IOP). The temporal response of ONH astrocytes (glial cells responsible for axonal support) to elevated IOP remains unknown. Here, we evaluate the response of actin-based astrocyte extensions and integrin-based signaling within the ONH to 8 hours of IOP elevation in a rat model. IOP elevation of 60 mm Hg was achieved under isoflurane anesthesia using anterior chamber cannulation connected to a saline reservoir...
2016: PloS One
https://www.readbyqxmd.com/read/27879274/cortactin-in-atherosclerosis-just-say-no
#4
EDITORIAL
Patrick Belvitch, Alicia N Rizzo, Steven M Dudek
No abstract text is available yet for this article.
December 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27864464/inhibition-of-stress-fiber-formation-preserves-blood-brain-barrier-after-intracerebral-hemorrhage-in-mice
#5
Anatol Manaenko, Peng Yang, Derek Nowrangi, Enkhjargal Budbazar, Richard E Hartman, Andre Obenaus, William J Pearce, John H Zhang, Jiping Tang
*Anatol Manaenko and Peng Yang contributed equally to this work.Intracerebral hemorrhage (ICH) represents the deadliest subtype of all strokes. The development of brain edema, a consequence of blood-brain barrier (BBB) disruption, is the most life-threatening event after ICH. Pathophysiological conditions activate the endothelium, one of the components of BBB, inducing rearrangement of the actin cytoskeleton. Upon activation, globular actin assembles into a filamentous actin resulting in the formation of contractile actin bundles, stress fibers...
November 18, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27864331/role-of-sphingosine-kinase-1-and-s1p-transporter-spns2-in-hgf-mediated-lamellipodia-formation-in-lung-endothelium
#6
Panfeng Fu, David L Ebenezer, Evgeny V Berdyshev, Irina A Bronova, Mark Shaaya, Anantha Harijith, Viswanathan Natarajan
Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation and motility of human lung microvascular endothelial cells (HLMVECs) via PI3k/Akt signal transduction and reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P1, in lamellipodia formation and perhaps motility of HLMVECs...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27825967/a-novel-splice-variant-of-supervillin-sv5-promotes-carcinoma-cell-proliferation-and-cell-migration
#7
Xueran Chen, Haoran Yang, Shangrong Zhang, Zhen Wang, Fang Ye, Chaozhao Liang, Hongzhi Wang, Zhiyou Fang
Supervillin is an actin-associated protein that regulates actin dynamics by interacting with Myosin II, F-actin, and Cortactin to promote cell contractility and cell motility. Two splicing variants of human Supervillin (SV1 and SV4) have been reported in non-muscle cells; SV1 lacks 3 exons present in the larger isoform SV4. SV2, also called archvillin, is present in striated muscle; SV3, also called smooth muscle archvillin or SmAV, was cloned from smooth muscle. In the present study, we identify a novel splicing variant of Supervillin (SV5)...
November 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27824079/mena-inv-dysregulates-cortactin-phosphorylation-to-promote-invadopodium-maturation
#8
Maxwell D Weidmann, Chinmay R Surve, Robert J Eddy, Xiaoming Chen, Frank B Gertler, Ved P Sharma, John S Condeelis
Invadopodia, actin-based protrusions of invasive carcinoma cells that focally activate extracellular matrix-degrading proteases, are essential for the migration and intravasation of tumor cells during dissemination from the primary tumor. We have previously shown that cortactin phosphorylation at tyrosine residues, in particular tyrosine 421, promotes actin polymerization at newly-forming invadopodia, promoting their maturation to matrix-degrading structures. However, the mechanism by which cells regulate the cortactin tyrosine phosphorylation-dephosphorylation cycle at invadopodia is unknown...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27805253/cortactin-contributes-to-the-tumorigenicity-of-colorectal-cancer-by-promoting-cell-proliferation
#9
Huo Wu, Xi Cheng, Xiaopin Ji, Yonggang He, Xiaoqian Jing, Haoxuan Wu, Ren Zhao
Cortactin is a scaffolding protein that regulates Arp2/3-mediated actin polymerization. We showed in a previous study that cortactin was highly expressed in human stage II-III colorectal cancer (CRC) tissues. In the present study, using colony formation and CCK-8 assays, we showed that overexpression of cortactin accelerated the proliferation of CRC cells. Flow cytometric assays revealed that cortactin promoted G1/S phase cell cycle transition. Later, we constructed the phosphorylation mutation of cortactin at the Tyr421 residue...
October 27, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27778524/the-actin-binding-proteins-cortactin-and-hs1-are-dispensable-for-platelet-actin-nodule-and-megakaryocyte-podosome-formation
#10
Steven G Thomas, Natalie S Poulter, Danai Bem, Brenda Finney, Laura M Machesky, Stephen P Watson
A dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cell types. In platelets and megakaryocytes, these proteins have been shown to be important for proper platelet production and function. The cortactin family of proteins (Cttn & HS1) are known to regulate WASp-Arp2/3-mediated actin polymerisation in other cell types and so here we address the role of these proteins in platelets using knockout mouse models...
October 25, 2016: Platelets
https://www.readbyqxmd.com/read/27771248/dynamin2-gtpase-contributes-to-invadopodia-formation-in-invasive-bladder-cancer-cells
#11
Yubai Zhang, Maya Nolan, Hiroshi Yamada, Masami Watanabe, Yasutomo Nasu, Kohji Takei, Tetsuya Takeda
Cancer cell invasion is mediated by actin-based membrane protrusions termed invadopodia. Invadopodia consist of "core" F-actin bundles associated with adhesive and proteolytic machineries promoting cell invasion by degrading extracellular matrix (ECM). Formation of the F-actin core in invadopodia is regulated by various actin-binding proteins including Arp2/3 complex and cortactin. Dynamin GTPase localizes to the invadopodia and is implicated in cancer cell invasion, but its precise role at the invadopodia remained elusive...
October 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27758765/amp-activated-protein-kinase-and-sirtuin-1-coregulation-of-cortactin-contributes-to-endothelial-function
#12
Tzu-Pin Shentu, Ming He, Xiaoli Sun, Jianlin Zhang, Fan Zhang, Brendan Gongol, Traci L Marin, Jiao Zhang, Liang Wen, Yinsheng Wang, Gregory G Geary, Yi Zhu, David A Johnson, John Y-J Shyy
OBJECTIVE: Cortactin translocates to the cell periphery in vascular endothelial cells (ECs) on cortical-actin assembly in response to pulsatile shear stress. Because cortactin has putative sites for AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) deacetylation, we examined the hypothesis that AMPK and SIRT1 coregulate cortactin dynamics in response to shear stress. APPROACH AND RESULTS: Analysis of the ability of AMPK to phosphorylate recombinant cortactin and oligopeptides whose sequences matched AMPK consensus sequences in cortactin pointed to Thr-401 as the site of AMPK phosphorylation...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27715391/regulation-of-lysosomal-phosphoinositide-balance-by-inpp5e-is-essential-for-autophagosome-lysosome-fusion
#13
Shuhei Nakamura, Junya Hasegawa, Tamotsu Yoshimori
Macroautophagy (autophagy) is a multistep intracellular degradation system. Autophagosomes form, mature, and ultimately fuse with lysosomes, where their sequestered cargo molecules are digested. In contrast to autophagosome formation, our knowledge of autophagosome-lysosome fusion is limited. In a recent study, we identified a novel regulator of autophagy, INPP5E (inositol polyphosphate-5-phosphatase E), which is essential for autophagosome-lysosome fusion. INPP5E primarily functions in neuronal cells, and knockdown of the corresponding gene causes accumulation of autophagosomes by impairing fusion with lysosomes...
October 7, 2016: Autophagy
https://www.readbyqxmd.com/read/27705916/asporin-enhances-colorectal-cancer-metastasis-through-activating-the-egfr-src-cortactin-signaling-pathway
#14
Huo Wu, Xiaoqian Jing, Xi Cheng, Yonggang He, Lei Hu, Haoxuan Wu, Feng Ye, Ren Zhao
Asporin has been implicated as an oncogene in various types of human cancers; however, the roles of asporin in the development and progression of colorectal cancer (CRC) have not yet been determined. With clinical samples, we found that asporin was highly expressed in CRC tissues compared to adjacent normal tissues and the asporin expression levels were significantly associated with lymph node metastasis status and TNM stage of the patients. Through knockdown of asporin in CRC cell lines RKO and SW620 or overexpression of asporin in cell lines HT-29 and LoVo, we found that asporin could enhance wound healing, migration and invasion abilities of the CRC cells...
September 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27705796/vegf-a-notch-induced-podosomes-proteolyse-basement-membrane-collagen-iv-during-retinal-sprouting-angiogenesis
#15
Pirjo Spuul, Thomas Daubon, Bettina Pitter, Florian Alonso, Isabelle Fremaux, IJsbrand Kramer, Eloi Montanez, Elisabeth Génot
During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane...
October 4, 2016: Cell Reports
https://www.readbyqxmd.com/read/27667566/role-of-end-binding-protein-1-in-endothelial-permeability-response-to-barrier-disruptive-and-barrier-enhancing-agonists
#16
Xinyong Tian, Tomomi Ohmura, Alok S Shah, Sophia Son, Yufeng Tian, Anna A Birukova
Rapid changes in microtubule (MT) polymerization dynamics affect regional activity of small GTPases RhoA and Rac1, which play a key role in the regulation of actin cytoskeleton and endothelial cell (EC) permeability. This study tested the role of End Binding Protein-1 (EB1) in the mechanisms of increased and decreased EC permeability caused by thrombin and hepatocyte growth factor (HGF) and mediated by RhoA and Rac1 GTPases, respectively. Stimulation of human lung EC with thrombin inhibited peripheral MT growth, which was monitored by morphological and biochemical evaluation of peripheral MT and the levels of stabilized MT...
September 23, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27646271/cancer-associated-mutations-in-the-protrusion-targeting-region-of-p190rhogap-impact-tumor-cell-migration
#17
Fabien Binamé, Aurélien Bidaud-Meynard, Laure Magnan, Léo Piquet, Bertille Montibus, Anne Chabadel, Frédéric Saltel, Valérie Lagrée, Violaine Moreau
Spatiotemporal regulation of RhoGTPases such as RhoA is required at the cell leading edge to achieve cell migration. p190RhoGAP (p190A) is the main negative regulator of RhoA and localizes to membrane protrusions, where its GTPase-activating protein (GAP) activity is required for directional migration. In this study, we investigated the molecular processes responsible for p190A targeting to actin protrusions. By analyzing the subcellular localization of truncated versions of p190A in hepatocellular carcinoma cells, we identified a novel functional p190A domain: the protrusion localization sequence (PLS) necessary and sufficient for p190A targeting to leading edges...
September 26, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27633051/cortactin-promotes-cell-migration-and-invasion-through-upregulation-of-the-dedicator-of-cytokinesis%C3%A2-1-expression-in-human-colorectal-cancer
#18
Xiaoqian Jing, Huo Wu, Xiaopin Ji, Haoxuan Wu, Minmin Shi, Ren Zhao
Cortactin (CTTN), a major substrate of the Src tyrosine kinase, has been implicated in cell proliferation, motility and invasion in various types of cancer. However, the molecular mechanisms of CTTN-driven malignant behavior remain unclear. In the current study, we determined the expression of CTTN in colorectal cancer and investigated its underlying mechanism in the metastasis of colorectal cancer. We confirmed increased CTTN expression in lymph node-positive CRC specimens and highly invasive CRC cell lines...
August 31, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27605702/moesin-and-cortactin-control-actin-dependent-multivesicular-endosome-biogenesis
#19
Olivia Muriel, Alejandra Tomas, Cameron C Scott, Jean Gruenberg
We have used in vivo and in vitro strategies to study the mechanisms of multivesicular endosomes biogenesis. We found that, while annexinA2 and Arp2/3 mediate F-actin nucleation and branching, respectively, the ERM protein moesin supports the formation of F-actin networks on early endosomes. We also found that moesin plays no role during endocytosis and recycling to the plasma membrane, but is absolutely required, much like actin, for early-to-late endosome transport and multivesicular endosome formation. Both actin network formation in vitro and early-to-late endosome transport in vivo also depend on the F-actin binding protein cortactin...
September 7, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27603901/pro-invasive-effect-of-proto-oncogene-pbf-is-modulated-by-an-interaction-with-cortactin
#20
Rachel J Watkins, Waraporn Imruetaicharoenchoke, Martin L Read, Neil Sharma, Vikki L Poole, Erica Gentillin, Sukhchain Bansal, Emy Bosseboeuf, Rachel Fletcher, Hannah R Nieto, Ujjal Mallick, Allan Hackshaw, Hisham Mehanna, Kristien Boelaert, Vicki E Smith, Christopher J McCabe
CONTEXT: Metastatic disease is responsible for the majority of endocrine cancer deaths. New therapeutic targets are urgently needed to improve patient survival rates. OBJECTIVE: The proto-oncogene PTTG1-Binding Factor (PBF/PTTG1IP) is overexpressed in multiple endocrine cancers and circumstantially associated with tumour aggressiveness. This study aimed to understand the role of PBF in tumour cell invasion and identify possible routes to inhibit its action. Design, Setting, Patients, and Interventions: Thyroid, breast and colorectal cells were transfected with PBF and cultured for in vitro analysis...
September 7, 2016: Journal of Clinical Endocrinology and Metabolism
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