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Cortactin

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https://www.readbyqxmd.com/read/29152154/cortactin-in-cancer-cell-migration-and-invasion
#1
REVIEW
Miao Yin, Wenqing Ma, Liguo An
Cortactin, a substrate of sarcoma (Src) kinases, is an actin-binding protein that is involved in cytoskeletal regulation, and is frequently overexpressed in cancer cells. Binding to the actin related protein 2/3 (Arp2/3) complex stimulates cortactin activity, which promotes F-actin nucleation and assembly. Cortactin promotes cancer cell migration and invasion, and plays a pivotal role in invadopodia formation and extra cellular matrix degradation. Overexpression of cortactin, by amplification of the chromosomal band 11q13, increases tumor aggressiveness...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133485/pyk2-and-fak-differentially-regulate-invadopodia-formation-and-function-in-breast-cancer-cells
#2
Alessandro Genna, Stefanie Lapetina, Nikola Lukic, Shams Twafra, Tomer Meirson, Ved P Sharma, John S Condeelis, Hava Gil-Henn
The nonreceptor tyrosine kinase Pyk2 is highly expressed in invasive breast cancer, but the mechanism by which it potentiates tumor cell invasiveness is unclear at present. Using high-throughput protein array screening and bioinformatic analysis, we identified cortactin as a novel substrate and interactor of proline-rich tyrosine kinase 2 (Pyk2). Pyk2 colocalizes with cortactin to invadopodia of invasive breast cancer cells, where it mediates epidermal growth factor-induced cortactin tyrosine phosphorylation both directly and indirectly via Src-mediated Abl-related gene (Arg) activation, leading to actin polymerization in invadopodia, extracellular matrix degradation, and tumor cell invasion...
November 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29121955/cd146-a-novel-target-of-cd44-signaling-suppresses-breast-tumor-cell-invasion
#3
Allal Ouhtit, Mohammed E Abdraboh, Andrew D Hollenbach, Hatem Zayed, Madhwa H G Raj
BACKGROUND: We have previously validated three novel CD44-downstream positively regulated transcriptional targets, including Cortactin, Survivin and TGF-β2, and further characterized the players underlying their separate signaling pathways. In the present study, we identified CD146 as a potential novel target, negatively regulated by CD44. While the exact function of CD146 in breast cancer (BC) is not completely understood, substantial evidence from our work and others support the hypothesis that CD146 is a suppressor of breast tumor progression...
November 9, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29107098/corticosteroid-induced-dendrite-loss-and-behavioral-deficiencies-can-be-blocked-by-activation-of-abl2-arg-kinase
#4
Lauren P Shapiro, Mitchell H Omar, Anthony J Koleske, Shannon L Gourley
Stressor exposure induces neuronal remodeling in specific brain regions. Given the persistence of stress-related illnesses, key next steps in determining the contributions of neural structure to mental health are to identify cell types that fail to recover from stressor exposure and to identify "trigger points" and molecular underpinnings of stress-related neural degeneration. We evaluated dendrite arbor structure on hippocampal CA1 pyramidal neurons before, during, and following prolonged exposure to one key mediator of the stress response - corticosterone (cortisol in humans)...
October 26, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29068555/diagnostic-utility-of-cortactin-antibodies-in-myasthenia-gravis
#5
REVIEW
Isabel Illa, Elena Cortés-Vicente, María Ángeles Martínez, Eduard Gallardo
Patients with myasthenia gravis (MG) without antibodies to the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) have been classified as having double-seronegative myasthenia gravis (dSNMG). We used the sera from six dSNMG patients with positive immunohistochemistry assays in a protein array to screen reactivity with 9000 human proteins. We identified cortactin, an intracellular protein that interacts with agrin/MuSK favoring AChR aggregation, as a new antigen in dSNMG. We then designed an in-house enzyme-linked immunosorbent assay as a screening assay and confirmed these results by western blot...
October 25, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29051140/fgd5-faciogenital-dysplasia-5-regulates-vegf-vascular-endothelial-growth-factor-a-receptor-2-coupling-to-pi3-phosphoinositide-3-kinase-and-receptor-recycling
#6
Maikel A Farhan, Abul K Azad, Nicolas Touret, Allan G Murray
OBJECTIVE: VEGF (vascular endothelial growth factor-A) signaling to the endothelial cell (EC) through VEGFR2 (VEGF receptor-2) is the principal cue driving new blood vessel formation. FGD5 (faciogenital dysplasia-5)-a Rho-family guanine nucleotide exchange factor-is selectively expressed in EC. Deficiency of FGD5 is embryonically lethal in mice and perturbs angiogenesis and VEGF signal transduction. However, the mechanism of FGD5 regulation of VEGF signaling is poorly understood. APPROACH AND RESULTS: Angiogenic sprouting and EC cytoskeletal remodeling were evaluated in a 3-dimensional (3D) in vitro model...
October 19, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28983097/tyrosine-dephosphorylated-cortactin-downregulates-contractility-at-the-epithelial-zonula-adherens-through-srgap1
#7
Xuan Liang, Srikanth Budnar, Shafali Gupta, Suzie Verma, Siew-Ping Han, Michelle M Hill, Roger J Daly, Robert G Parton, Nicholas A Hamilton, Guillermo A Gomez, Alpha S Yap
Contractile adherens junctions support cell-cell adhesion, epithelial integrity, and morphogenesis. Much effort has been devoted to understanding how contractility is established; however, less is known about whether contractility can be actively downregulated at junctions nor what function this might serve. We now identify such an inhibitory pathway that is mediated by the cytoskeletal scaffold, cortactin. Mutations of cortactin that prevent its tyrosine phosphorylation downregulate RhoA signaling and compromise the ability of epithelial cells to generate a contractile zonula adherens...
October 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28972183/the-actin-related-p41arc-subunit-contributes-to-p21-activated-kinase-1-pak1-mediated-glucose-uptake-into-skeletal-muscle-cells
#8
Ragadeepthi Tunduguru, Jing Zhang, Arianne Aslamy, Vishal A Salunkhe, Joseph T Brozinick, Jeffrey S Elmendorf, Debbie C Thurmond
Defects in translocation of the glucose transporter GLUT4 are associated with peripheral insulin resistance, pre-clinical diabetes, and progression to type 2 diabetes. GLUT4 recruitment to the plasma membrane of skeletal muscle cells requires filamentous (F)-actin remodeling. Insulin signaling in muscle requires p21-activated kinase-1 (PAK1), whose downstream signaling triggers actin remodeling that promotes GLUT4 vesicle translocation and glucose uptake into skeletal muscle cells. Actin remodeling is a cyclic process, and while PAK1 is known to initiate changes to the cortical actin-binding protein cofilin to stimulate the depolymerizing arm of the cycle, how PAK1 might trigger the polymerizing arm of the cycle remains unresolved...
September 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28916556/cell-scientist-to-watch-paul-timpson
#9
(no author information available yet)
Paul Timpson received his bachelor's degree from the University of Strathclyde, UK and completed his PhD under the supervision of Margaret Frame at the Beatson Institute for Cancer Research and the University of Glasgow in 2002, working on Src kinases and Rho family GTPases in cancer cell invasion. He then moved to the Garvan Institute of Medical Research in Sydney, Australia to work with Roger Daly on the actin-binding protein cortactin in several cancer models. Paul returned to the Beatson Institute in 2007 with the aid of an AstraZeneca postdoctoral research fellowship...
September 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28889177/a-15-amino-acid-c-terminal-peptide-of-beta-defensin-3-inhibits-bone-resorption-by-inhibiting-the-osteoclast-differentiation-and-disrupting-podosome-belt-formation
#10
Ok-Jin Park, Jiseon Kim, Ki Bum Ahn, Jue Yeon Lee, Yoon-Jeong Park, Kee-Yeon Kum, Cheol-Heui Yun, Seung Hyun Han
Human beta-defensin-3 (HBD3), which is secreted from cells in the skin, salivary gland, and bone marrow, exhibits antimicrobial and immunomodulatory activities. Its C-terminal end contains a 15-amino acid polypeptide (HBD3-C15) that is known to effectively elicit antimicrobial activity. Recently, certain antimicrobial peptides are known to inhibit osteoclast differentiation and, thus, we investigated whether HBD3-C15 hinders osteoclast differentiation and bone destruction to assess its potential use as an anti-bone resorption agent...
December 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28885660/cortactin-and-phosphorylated-cortactin-tyr421-and-tyr466-expression-in-supraglottic-laryngeal-carcinomas-and-lymph-node-metastases
#11
Gino Marioni, Marco Lionello, Rosario Marchese-Ragona, Elena Fasanaro, Elisa Valentini, Elisabetta Zanoletti, Paola Stritoni, Giulia Ramacciotti, Vincenza Guzzardo, Luciano Giacomelli, Giovanni Ralli, Giancarlo Ottaviano, Stella Blandamura
BACKGROUND: The most important adverse prognostic factor for laryngeal squamous cell carcinoma (LSCC) is the presence of cervical lymph node metastases. The supraglottic area of the larynx is richly supplied with lymphatics, and 25%-75% of supraglottic carcinomas metastasize in neck lymph nodes. Cortactin is a multidomain protein related to actin cytoskeleton regulation, podosome and lamellipodia formation, integrin signaling, axon guidance and extracellular matrix degradation. Cortactin is involved in metastasis formation because of its role in cell mobility...
September 5, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28769876/candida-albicans-the-ability-to-invade-epithelial-cells-and-survive-under-oxidative-stress-is-unlinked-to-hyphal-length
#12
Paloma K Maza, Alexis Bonfim-Melo, Ana C B Padovan, Renato A Mortara, Cristina M Orikaza, Lilian M Damas Ramos, Tauany R Moura, Frederico M Soriani, Ricardo S Almeida, Erika Suzuki, Diana Bahia
In its hyphal form, Candida albicans invades epithelial and endothelial cells by two distinct mechanisms: active penetration and induced endocytosis. The latter is dependent on a reorganization of the host cytoskeleton (actin/cortactin recruitment), whilst active penetration does not rely on the host's cellular machinery. The first obstacle for the fungus to reach deep tissues is the epithelial barrier and this interaction is crucial for commensal growth, fungal pathogenicity and host defense. This study aimed to characterize in vitro epithelial HeLa cell invasion by four different isolates of C...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28759570/camp-dependent-activation-of-protein-kinase-a-attenuates-respiratory-syncytial-virus-induced-human-airway-epithelial-barrier-disruption
#13
Fariba Rezaee, Terri J Harford, Debra T Linfield, Ghaith Altawallbeh, Ronald J Midura, Andrei I Ivanov, Giovanni Piedimonte
Airway epithelium forms a barrier to the outside world and has a crucial role in susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an important second messenger acting via two intracellular signaling molecules: protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We sought to investigate effects of increased cAMP level on the disruption of model airway epithelial barrier caused by RSV infection and the molecular mechanisms underlying cAMP actions. Human bronchial epithelial cells were infected with RSV-A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs...
2017: PloS One
https://www.readbyqxmd.com/read/28692057/the-interactome-of-metabolic-enzyme-carbonic-anhydrase-ix-reveals-novel-roles-in-tumor-cell-migration-and-invadopodia-mmp14-mediated-invasion
#14
M Swayampakula, P C McDonald, M Vallejo, E Coyaud, S C Chafe, A Westerback, G Venkateswaran, J Shankar, G Gao, E M N Laurent, Y Lou, K L Bennewith, C T Supuran, I R Nabi, B Raught, S Dedhar
Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX 'interactome' in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins with potential roles in tumor progression. High confidence proteins identified include metabolic transporters, β1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14 (MMP14)...
November 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28663723/huntingtin-interacting-protein-1-related-protein-plays-a-critical-role-in-dendritic-development-and-excitatory-synapse-formation-in-hippocampal-neurons
#15
Lin Peng, Qian Yang, Xingxing Xu, Yonglan Du, Yu Wu, Xiaofang Shi, Junyu Xu, Lijun Zhu, Jianhong Luo
Huntingtin-interacting protein 1-related (HIP1R) protein is considered to be an endocytic adaptor protein like the other two members of the Sla2 family, Sla2p and HIP1. They all contain homology domains responsible for the binding of clathrin, inositol lipids and F-actin. Previous studies have revealed that HIP1R is highly expressed in different regions of the mouse brain and localizes at synaptic structures. However, the function of HIP1R in the nervous system remains unknown. In this study, we investigated HIP1R function in cultured rat hippocampal neurons using an shRNA knockdown approach...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28528353/adrenomedullin-ameliorates-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro-and-in-vivo-through-modulation-of-rho-gtpases
#16
Nan Dong, Lixia Meng, Ruqun Xue, Meng Yu, Zhonghua Zhao, Xueguang Liu
PURPOSE: Podocyte injury is a key event in proteinuric kidney disease and eventually glomerular scarring. While adrenomedullin (AM), a potent vasodilatory peptide, has been reported to confer renoprotection in several experimental models of kidney diseases, its effect on injured podocytes and the related mechanism is still largely unknown. METHODS: Employing Western blotting analysis, immunoprecipitation and immunofluorescence, we investigated the effects of AM on the expressions of podocyte cytoskeletal proteins and Rho-family small GTPases (Rho GTPases) in puromycin aminonucleoside (PAN)-induced podocyte injury, both in cultured podocytes and in PAN nephrosis rats...
August 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28522963/the-f-actin-binding-protein-cortactin-regulates-the-dynamics-of-the-exocytotic-fusion-pore-through-its-sh3-domain
#17
Arlek M González-Jamett, María J Guerra, María J Olivares, Valentina Haro-Acuña, Ximena Baéz-Matus, Jacqueline Vásquez-Navarrete, Fanny Momboisse, Narcisa Martinez-Quiles, Ana M Cárdenas
Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca(2+) signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28484055/endothelial-cd2ap-binds-the-receptor-icam-1-to-control-mechanosignaling-leukocyte-adhesion-and-the-route-of-leukocyte-diapedesis-in-vitro
#18
Antje Schaefer, Trynette J van Duijn, Jisca Majolee, Keith Burridge, Peter L Hordijk
Inflammation is driven by excessive transmigration (diapedesis) of leukocytes from the blood to the tissue across the endothelial cell monolayer that lines blood vessels. Leukocyte adhesion, crawling, and transmigration are regulated by clustering of the endothelial mechanosensitive receptor intercellular adhesion molecule-1 (ICAM-1). Whereas several proteins are known to promote ICAM-1 function, the molecular mechanisms that limit ICAM-1-mediated adhesion to prevent excessive leukocyte transmigration remain unknown...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#19
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#20
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
The role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function is unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysaccharide (LPS). Receptor screening using pharmacological and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
June 15, 2017: Molecular Biology of the Cell
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