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https://www.readbyqxmd.com/read/29464017/regulation-of-e-cadherin-localization-by-microtubule-targeting-agents-rapid-promotion-of-cortical-e-cadherin-through-p130cas-src-inhibition-by-eribulin
#1
Nicholas F Dybdal-Hargreaves, April L Risinger, Susan L Mooberry
Microtubule targeting agents (MTAs) are some of the most effective anticancer drugs used to treat a wide variety of adult and pediatric cancers. Building evidence suggests that these drugs inhibit interphase signaling events and that this contributes to their anticancer actions. The effects of diverse MTAs were evaluated following a 2 hour incubation with clinically relevant concentrations to test the hypothesis that these drugs rapidly and differentially disrupt epithelial-to-mesenchymal transition (EMT)-related signaling...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29436609/enhancement-of-malignant-properties-of-human-glioma-cells-by-ganglioside-gd3-gd2
#2
Taiji Iwasawa, Pu Zhang, Yuki Ohkawa, Hiroyuki Momota, Toshihiko Wakabayashi, Yuhsuke Ohmi, Robiul H Bhuiyan, Keiko Furukawa, Koichi Furukawa
Sialic acid-containing glycosphingolipids, gangliosides, are considered as cancer associated antigens in neuro-ectoderm-derived tumors such as melanomas and neuroblastomas. In particular, gangliosides GD3 and GD2 are expressed in human gliomas. It has been reported that their expression levels increase along with increased malignant properties. However, the implication of GD3/GD2 in human glioma cells has never been clarified, at least to the best of our knowledge. In this study, we introduced the cDNA of GD3 synthase (GD3S)(ST8SIA1) into a glioma cell line, U-251MG, that expresses neither GD3 nor GD2, thereby establishing transfectant cells U-251MG-GD3S(+) expressing high levels of GD3 and GD2 on the cell surface...
February 7, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29364471/expression-of-three-proteins-in-endometrioid-adenocarcinoma-and-their-significance-in-clinical-nursing-diagnosis-and-treatment
#3
X-Y Yin, X Yang, Y Cui, S-M Zhang
OBJECTIVE: This study aimed to investigate the role of NEDD9 (neural precursor cell expressed developmentally down-regulated 9), BCAR1/P130CAS (BCAR1/P130 Crk-associated substrate) and paxillin in predicting the prognosis of endometrioid adenocarcinoma (EA), so as to guild the nursing of EA. PATIENTS AND METHODS: A total of 65 patients who visited Affiliated Hongqi Hospital of Mudanjiang Medical University between June 2015 and June 2017 were enrolled. They underwent gynecological surgery and had their EA confirmed by pathology, and they were assigned to the EA group...
January 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29304771/high-bcar1-expression-is-associated-with-early-psa-recurrence-in-erg-negative-prostate-cancer
#4
Asmus Heumann, Nina Heinemann, Claudia Hube-Magg, Dagmar S Lang, Katharina Grupp, Martina Kluth, Sarah Minner, Christina Möller-Koop, Markus Graefen, Hans Heinzer, Maria Christina Tsourlakis, Waldemar Wilczak, Corinna Wittmer, Frank Jacobsen, Hartwig Huland, Ronald Simon, Thorsten Schlomm, Guido Sauter, Stefan Steurer, Patrick Lebok, Andrea Hinsch
BACKGROUND: Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. METHODS: To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples. BCAR1 expression levels were compared with clinical characteristics, PSA recurrence, molecular subtype defined by ERG status and 3p, 5q, 6q and PTEN deletion. RESULTS: BCAR1 staining was barely detectable in normal prostate glands but seen in 77...
January 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29196262/collagen-vi-suppresses-fibronectin-induced-enteric-neural-crest-cell-migration-by-downregulation-of-focal-adhesion-proteins
#5
Shoichi Nishida, Hisayoshi Yoshizaki, Yoshitomo Yasui, Tsuyoshi Kuwahara, Etsuko Kiyokawa, Miyuki Kohno
The enteric nervous system (ENS) is a network of neurons and glia that are derived from enteric neural crest cells (ENCCs) and essential for regulating peristaltic activity of the colon. ENCCs migrate along the gastrointestinal tract to form the ENS, and disruption of ENCC motility leads to ENS disorders, such as Hirschsprung's disease. Previous ENCC-transplant experiments show that ENCCs can invade into isolated mouse intestines by age E13.5, but not after E15.5. We hypothesized that altered age-specific micro-environments in the intestine are responsible for ENCC invasion/migration...
January 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29167336/an-insight-into-the-role-of-e3-ubiquitin-ligase-c-cbl-escrt-machinery-and-host-cell-signaling-in-kaposi-s-sarcoma-associated-herpesvirus-kshv-entry-and-trafficking
#6
Binod Kumar, Arunava Roy, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal endothelial cell begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), xCT and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multi-molecular complex of receptors, signal molecules (FAK, Src, PI3-K, RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas and GEF-C3G), and actin/myosin II light chain that leads to virus entry via macropinocytosis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29132432/ac-93253-iodide-a-novel-src-inhibitor-suppresses-nsclc-progression-by-modulating-multiple-src-related-signaling-pathways
#7
Yi-Hua Lai, Sih-Yin Lin, Yu-Shan Wu, Huei-Wen Chen, Jeremy J W Chen
BACKGROUND: The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds. METHODS: Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment...
November 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29074139/optogenetic-control-of-focal-adhesion-kinase-signaling
#8
Maximilian Hörner, Claire Chatelle, Wignand W D Mühlhäuser, David R Stocker, Michael Coats, Wilfried Weber, Gerald Radziwill
Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor receptors and mechanical stress to control cell adhesion, motility, survival and proliferation. Here, we developed a single-component, photo-activatable FAK, termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2 (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from physiological stimuli and activates downstream signaling rapidly and reversibly upon blue light exposure. OptoFAK stimulates SRC creating a positive feedback loop on FAK activation, facilitating phosphorylation of paxillin and p130Cas in adherent cells...
October 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29039492/black-rice-derived-anthocyanins-inhibit-her-2-positive-breast-cancer-epithelial-mesenchymal-transition-mediated-metastasis-in%C3%A2-vitro-by-suppressing-fak-signaling
#9
Jie Zhou, Yan-Feng Zhu, Xiang-Yan Chen, Bin Han, Fei Li, Jing-Yao Chen, Xiao-Li Peng, Li-Ping Luo, Wei Chen, Xiao-Ping Yu
This study aimed to investigate the role of focal adhesion kinase (FAK) signaling in the inhibitory effects of black rice anthocyanins (BRACs) on human epidermal growth factor receptor-2 (HER-2)-positive human breast cancer cell metastasis, using the MCF-10A, MCF-7 and MDA-MB-453 cells. BRACs exerted an anti-metastatic effect on the HER-2-positive breast cancer cells. The effects of BRACs on the proliferation of the MDA-MB-453 cells were examined by cell counting kit-8 assay. A wound-healing assay was used to examine the effects of BRACs on the migration of the breast cancer cells...
October 11, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28977999/platelet-derived-growth-factor-c-promotes-human-melanoma-aggressiveness-through-activation-of-neuropilin-1
#10
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912559/inherent-aggressive-character-of-invasive-and-non-invasive-cells-dictates-the-in-vitro-migration-pattern-of-multicellular-spheroid
#11
Sukanya Gayan, Abhishek Teli, Tuli Dey
Cellular migration, a process relevant to metastasis, is mostly studied in the conventional 2D condition. However, cells cultured in the 3D condition assumed to mimic the in vivo conditions better. The current study is designed to compare an invasive and non-invasive adenocarcinoma cell with an invasive fibrosarcoma cell to understand the migration pattern of the multicellular spheroid. It is observed that conventional haplotaxis, chemotactic and pseudo-3D migration assay cannot distinguish between the invasive and non-invasive cells conclusively under 2D condition...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28860193/structural-and-functional-insights-into-the-interaction-between-the-cas-family-scaffolding-protein-p130cas-and-the-focal-adhesion-associated-protein-paxillin
#12
Chi Zhang, Darcie J Miller, Cristina D Guibao, Dominique M Donato, Steven K Hanks, Jie J Zheng
The Cas family scaffolding protein p130Cas is a Src substrate localized in focal adhesions (FAs) and functions in integrin signaling to promote cell motility, invasion, proliferation, and survival. p130Cas targeting to FAs is essential for its tyrosine phosphorylation and downstream signaling. Although the N-terminal SH3 domain is important for p130Cas localization, it has also been reported that the C-terminal region is involved in p130Cas FA targeting. The C-terminal region of p130Cas or Cas family homology domain (CCHD) has been reported to adopt a structure similar to that of the focal adhesion kinase C-terminal focal adhesion-targeting domain...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28835419/glomerular-mesangial-cell-recruitment-and-function-requires-the-co-receptor-neuropilin-1
#13
Christina Swan Bartlett, Rizaldy Paz Scott, Isabel Anna Carota, Monika L Wnuk, Yashpal S Kanwar, Jeffrey H Miner, Susan E Quaggin
Proteinuria has been reported in cancer patients receiving agents that target the transmembrane receptor neuropilin-1 (Nrp1) suggesting potential adverse effects on glomerular function. Here we show that Nrp1 is highly expressed by mesangial cells and that genetic deletion of the Nrp1 gene from PDGFR+ mesangial cells results in proteinuric disease and glomerulosclerosis, leading to renal failure and death within 6 weeks of age in mice. The major defect is a failure of mesangial cell migration that is required to establish the mature glomerular tuft...
August 23, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28817661/ouabain-affects-cell-migration-via-na-k-atpase-p130cas-and-via-nucleus-centrosome-association
#14
Young Ou, Chen Xuan Pan, Jeremy Zuo, Frans A van der Hoorn
Na,K-ATPase is a membrane protein that catalyzes ATP to maintain transmembrane sodium and potassium gradients. In addition, Na,K-ATPase also acts as a signal-transducing receptor for cardiotonic steroids such as ouabain and activates a number of signalling pathways. Several studies report that ouabain affects cell migration. Here we used ouabain at concentrations far below those required to block Na,K-ATPase pump activity and show that it significantly reduced RPE cell migration through two mechanisms. It causes dephosphorylation of a 130 kD protein, which we identify as p130cas...
2017: PloS One
https://www.readbyqxmd.com/read/28730470/dissecting-kinase-effector-signaling-using-the-raprtap-methodology
#15
Anne-Marie Ray, Jennifer E Klomp, Kerrie B Collins, Andrei V Karginov
Kinases are involved in a broad spectrum of cell behaviors. A single kinase can interact with different ligands each eliciting a specific cellular response. Dissecting downstream signaling pathways of kinases is a key step to understanding physiological and pathological cell process. However, directing kinase activity to specific substrates remains challenging. Here, we present a new tool to selectively activate a kinase in a specific protein complex in living cells. This technology uses a rapamycin-inducible kinase activation coupled to interaction with FKBP12-binding domain (FRB) tagged protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28723560/crkl-mediates-p110%C3%AE-dependent-pi3k-signaling-in-pten-deficient-cancer-cells
#16
Jing Zhang, Xueliang Gao, Fabienne Schmit, Guillaume Adelmant, Michael J Eck, Jarrod A Marto, Jean J Zhao, Thomas M Roberts
The p110β isoform of PI3K is preferentially activated in many tumors deficient in the phosphatase and tensin homolog (PTEN). However, the mechanism(s) linking PTEN loss to p110β activation remain(s) mysterious. Here, we identify CRKL as a member of the class of PI3Kβ-interacting proteins. Silencing CRKL expression in PTEN-null human cancer cells leads to a decrease in p110β-dependent PI3K signaling and cell proliferation. In contrast, CRKL depletion does not impair p110α-mediated signaling. Further study showed that CRKL binds to tyrosine-phosphorylated p130Cas in PTEN-null cancer cells...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28700345/platelet-derived-growth-factor-c-promotes-human-melanoma-aggressiveness-through-activation-of-neuropilin-1
#17
Federica Ruffini, Lauretta Levati, Grazia Graziani, Simona Caporali, Maria Grazia Atzori, Stefania D'Atri, Pedro M Lacal
Despite recent progress in advanced melanoma therapy, identification of signalling pathways involved in melanoma switch from proliferative to invasive states is still crucial to uncover new therapeutic targets for improving the outcome of metastatic disease. Neuropilin-1 (NRP-1), a co-receptor for vascular endothelial growth factor-A (VEGF-A) tyrosine kinase receptors (VEGFRs), has been suggested to play a relevant role in melanoma progression. NRP-1 can be activated by VEGF-A also in the absence of VEGFRs, triggering specific signal transduction pathways (e...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28687864/stressed-podocytes-mechanical-forces-sensors-signaling-and-response
#18
REVIEW
Karlhans Endlich, Felix Kliewe, Nicole Endlich
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28608180/montelukast-improves-the-changes-of-cytoskeletal-and-adaptor-proteins-of-human-podocytes-by-interleukin-13
#19
Tae-Sun Ha, Ja Ae Nam, Su-Bin Seong, Moin A Saleem, Se Jin Park, Jae Il Shin
OBJECTIVE AND DESIGN: Interleukin-13 (IL-13) has recently been reported to be a potential cytokine in the pathogenesis of minimal-change nephrotic syndrome (MCNS). However, the mechanistic insights associated with podocyte dysfunction mediated by IL-13-induced changes in various slit diaphragm (SD) and cytoskeletal molecules have not yet been shown in cultured human podocytes in vitro. MATERIALS: Human conditionally immortalized podocytes were used. TREATMENT: Podocytes were incubated with various concentrations of IL-13 during the indicated time periods (6, 12, and 24 h) and montelukast was administered with the dose of 0...
September 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28442738/dysregulation-of-blimp1-transcriptional-repressor-unleashes-p130cas-erbb2-breast-cancer-invasion
#20
Marianna Sciortino, Maria Del Pilar Camacho-Leal, Francesca Orso, Elena Grassi, Andrea Costamagna, Paolo Provero, Wayne Tam, Emilia Turco, Paola Defilippi, Daniela Taverna, Sara Cabodi
ErbB2 overexpression is detected in approximately 20% of breast cancers and is correlated with poor survival. It was previously shown that the adaptor protein p130Cas/BCAR1 is a crucial mediator of ErbB2 transformation and that its overexpression confers invasive properties to ErbB2-positive human mammary epithelial cells. We herein prove, for the first time, that the transcriptional repressor Blimp1 is a novel mediator of p130Cas/ErbB2-mediated invasiveness. Indeed, high Blimp1 expression levels are detected in invasive p130Cas/ErbB2 cells and correlate with metastatic status in human breast cancer patients...
April 25, 2017: Scientific Reports
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