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https://www.readbyqxmd.com/read/29351406/interleukin-6-promotes-a-sustained-loss-of-endothelial-barrier-function-via-janus-kinase-mediated-stat3-phosphorylation-and-de-novo-protein-synthesis
#1
Hiba Alsaffar, Nina Martino, Joshua P Garrett, Alejandro P Adam
Vascular leakage is a hallmark of the inflammatory response. Acute changes in endothelial permeability are due to post-translational changes in intercellular adhesion and cytoskeleton proteins. However, little is known about the mechanisms leading to long-term changes in vascular permeability. Here, we show that Interleukin-6 (IL-6) promotes an increase in endothelial monolayer permeability that lasts over 24 h and demonstrate that activation of Src and MEK/Erk pathways are required only for short-term increases in permeability, being dispensable after 2 h...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29348675/stac2-negatively-regulates-osteoclast-formation-by-targeting-the-rank-signaling-complex
#2
Eutteum Jeong, Han Kyoung Choi, Jin Hee Park, Soo Young Lee
The receptor activator of nuclear factor-κB (RANK) protein activates various protein kinase signaling cascades, including those involving NF-κB, mitogen-activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine-protein kinase Tec. However, the mechanism underlying the negative regulation of RANK by downstream signaling molecules remains unclear. Here, we report that Src homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a novel RANK ligand-inducible protein that negatively regulates RANK-mediated osteoclast formation...
January 18, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29348492/v-src-driven-transformation-is-due-to-chromosome-abnormalities-but-not-src-mediated-growth-signaling
#3
Takuya Honda, Mariko Morii, Yuji Nakayama, Ko Suzuki, Noritaka Yamaguchi, Naoto Yamaguchi
v-Src is the first identified oncogene product and has a strong tyrosine kinase activity. Much of the literature indicates that v-Src expression induces anchorage-independent and infinite cell proliferation through continuous stimulation of growth signaling by v-Src activity. Although all of v-Src-expressing cells are supposed to form transformed colonies, low frequencies of v-Src-induced colony formation have been observed so far. Using cells that exhibit high expression efficiencies of inducible v-Src, we show that v-Src expression causes cell-cycle arrest through p21 up-regulation despite ERK activation...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348482/egfr-activation-triggers-cellular-hypertrophy-and-lysosomal-disease-in-naglu-depleted-cardiomyoblasts-mimicking-the-hallmarks-of-mucopolysaccharidosis-iiib
#4
Valeria De Pasquale, Antonio Pezone, Patrizia Sarogni, Alfonso Tramontano, Gabriele Giacomo Schiattarella, Vittorio Enrico Avvedimento, Simona Paladino, Luigi Michele Pavone
Mucopolysaccharidosis (MPS) IIIB is an inherited lysosomal storage disease caused by the deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU) required for heparan sulfate (HS) degradation. The defective lysosomal clearance of undigested HS results in dysfunction of multiple tissues and organs. We recently demonstrated that the murine model of MPS IIIB develops cardiac disease, valvular abnormalities, and ultimately heart failure. To address the molecular mechanisms governing cardiac dysfunctions in MPS IIIB, we generated a model of the disease by silencing NAGLU gene expression in H9C2 rat cardiomyoblasts...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348460/fyn-promotes-mesenchymal-phenotypes-of-basal-type-breast-cancer-cells-through-stat5-notch2-signaling-node
#5
Ga-Hang Lee, Ki-Chun Yoo, Yoojeong An, Hae-June Lee, Minyoung Lee, Nizam Uddin, Min-Jung Kim, In-Gyu Kim, Yongjoon Suh, Su-Jae Lee
Basal type breast cancer is the most aggressive and has mesenchymal features with a high metastatic ability. However, the signaling node that determines the basal type features in breast cancer remains obscure. Here, we report that FYN among SRC family kinases is required for the maintenance of basal type breast cancer subtype. Importantly, FYN enhanced NOTCH2 activation in basal type breast cancer cells through STAT5-mediated upregulation of Jagged-1 and DLL4 NOTCH ligands, thereby contributed to mesenchymal phenotypes...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29345428/traf3-regulation-of-inhibitory-signaling-pathways-in-b-and-t-lymphocytes-by-kinase-and-phosphatase-localization
#6
REVIEW
Alicia M Wallis, Gail A Bishop
This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345412/wnt5a-promotes-migration-and-invasion-of-human-osteosarcoma-cells-via-src-erk-mmp-14-pathway
#7
Xingwen Wang, Xin Zhao, Zhigang Yi, Bing Ma, Hong Wang, Yanchuan Pu, Jing Wang, Shuanke Wang
WNT5A, a representative ligand of activating several non-canonical Wnt signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non-receptor tyrosine kinase SRC is required for WNT5A-induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings...
January 18, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29345355/effects-of-antioxidants-on-apoptosis-induced-by-dasatinib-and-nilotinib-in-k562-cells
#8
Sara Damiano, Serena Montagnaro, Maria Valeria Puzio, Lorella Severino, Ugo Pagnini, Marcella Barbarino, Daniele Cesari, Antonio Giordano, Salvatore Florio, Roberto Ciarcia
In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation and apoptosis...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29343154/dasatinib-induced-pulmonary-arterial-hypertension-a-rare-late-complication
#9
Uroosa Ibrahim, Amina Saqib, Vidhya Dhar, Marcel Odaimi
Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary arterial hypertension is defined by an increase in mean pulmonary arterial pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been reported in less than 1% of patients on chronic dasatinib treatment for chronic myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be categorized as either group 1 (drug-induced) or group 5 based on various mechanisms that may be involved including the pathogenesis of the disease process of chronic myelogenous leukemia...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29340103/anti-neoplastic-drugs-increase-caveolin-1-dependent-migration-invasion-and-metastasis-of-cancer-cells
#10
Natalia I Díaz-Valdivia, Claudia C Calderón, Jorge E Díaz, Lorena Lobos-González, Hugo Sepulveda, Rina J Ortíz, Samuel Martinez, Veronica Silva, Horacio J Maldonado, Patricio Silva, Sergio Wehinger, Verónica A Burzio, Vicente A Torres, Martín Montecino, Lisette Leyton, Andrew F G Quest
Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340070/a-novel-orally-available-syk-src-jak2-inhibitor-sklb-850-showed-potent-anti-tumor-activities-in-b-cell-lymphoma-bcl-models
#11
Nannan Zhang, Guo Zhang, Ning Liu, Wanting Lin, Sen Ji, Mingwu Zheng, Kai Chen, Xiao Liang, Guobo Li, Yu Ma, Jun Zhu, Ting Niu, Lin-Li Li, Jiong Li, Yu-Quan Wei, Sheng-Yong Yang
B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as potential targets for the treatment of BCL. We have recently developed a multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The aim of this study is to investigate the anti-BCL activities and mechanisms of action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850 significantly inhibited BCL cell proliferation, and induced apoptosis of BCL cells...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29335257/staphylococcal-superantigens-use-lama2-as-a-coreceptor-to-activate-t-cells
#12
Zhigang Li, Joseph J Zeppa, Mark A Hancock, John K McCormick, Terence M Doherty, Geoffrey N Hendy, Joaquín Madrenas
Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR signaling by activating an alternative pathway that is independent of LCK and utilizes a Gα11-containing G protein-coupled receptor (GPCR) leading to PLCβ activation. The molecules linking the superantigen to GPCR signaling are unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, the α2 subunit of the extracellular matrix protein laminin, as the coreceptor for staphylococcal superantigens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29334406/dasatinib-induced-pulmonary-arterial-hypertension
#13
REVIEW
Nurgül Özgür Yurttaş, Ahmet Emre Eşkazan
Drug-induced (Group 1) pulmonary hypertension (PH) is an important subgroup of PH involving dasatinib as a likely related agent, which is a second-generation tyrosine kinase inhibitor (TKI), that is used in the treatment of chronic myeloid leukemia (CML). The mechanism of dasatinib-induced pulmonary arterial hypertension (PAH) is unclear. However, the occurence of PAH at a late onset in CML patients suggests a chronic pathological mechanism with an insidious onset rather than an acute inflammatory or cardiac etiology...
January 15, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29330344/parathyroid-hormone-related-protein-exhibits-antioxidant-features-in-osteoblastic-cells-through-its-n-terminal-and-osteostatin-domains
#14
S Portal-Núñez, J A Ardura, D Lozano, I Martínez de Toda, M De la Fuente, G Herrero-Beaumont, R Largo, P Esbrit
OBJECTIVES: Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain...
January 2018: Bone & Joint Research
https://www.readbyqxmd.com/read/29327067/overexpression-of-nogo-receptor-3-ngr3-correlates-with-poor-prognosis-and-contributes-to-the-migration-of-epithelial-cells-of-nasopharyngeal-carcinoma-patients
#15
Jiang-Yi He, Ping Han, Yu Zhang, Yong-Dong Liu, Shi-Jian Song, Guo-Kai Feng, Yu An, Ai-Jun Zhou, Hong-Bo Wang, Li Yuan, Zhi-Rui Lin, Tian-Liang Xia, Man-Zhi Li, Yan-Min Liu, Xiao-Ming Huang, Hua Zhang, Qian Zhong
Lymph node metastasis (N classification) is one of the most important prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is associated with the transition of the N category in NPC patients. Although the nervous system has been reported to participate in many types of cancer progression, its functions in NPC progression remains unknown. Through analysis of gene profiling data, we demonstrate an enrichment of genes associated with neuronal development and differentiation in NPC tissues and cell lines...
January 11, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29324735/influence-of-c-src-on-hypoxic-resistance-to-paclitaxel-in-human-ovarian-cancer-cells-and-reversal-of-fv-429
#16
Qinglong Guo, Lu Lu, Yan Liao, Xiaoping Wang, Yi Zhang, Yicheng Liu, Shaoliang Huang, Haopeng Sun, Zhiyu Li, Li Zhao
SRC family kinase was documented to have vital roles in adjusting cancer cell malignant behaviors. To date, the role of c-Src, a member of SRC family kinase, in resistance to paclitaxel in human ovarian cancer cells under hypoxia has not been investigated. In the present study, we discovered that hypoxic environment suppressed paclitaxel-induced G2/M phase arrest and blockade of c-Src improved ovarian cancer cells' sensitivity to paclitaxel. FV-429, a derivative of natural flavonoid wogonin, could suppress gene expression and activation of c-Src, followed by deteriorated Stat3 nuclear translocation and its binding to HIF-1α, resulting in paclitaxel resistance reversal through G2/M arrest potentiation...
January 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29323185/biogenesis-of-podosome-rosettes-through-fission
#17
Szu-Lin Kuo, Chien-Lin Chen, Yi-Ru Pan, Wen-Tai Chiu, Hong-Chen Chen
Podosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Individual podosomes are often found to organize into large rosette-like structures in some types of cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and certain highly invasive cancer cells. In this study, we show that new podosome rosettes arise through one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318780/the-synergistic-role-of-atp-dependent-drug-efflux-pump-and-focal-adhesion-signaling-pathways-in-vinorelbine-resistance-in-lung-cancer
#18
Takao Nakanishi, Toshi Menju, Shigeto Nishikawa, Koji Takahashi, Ryo Miyata, Kei Shikuma, Terumasa Sowa, Naoto Imamura, Masatsugu Hamaji, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Toyofumi F Chen-Yoshikawa, Makoto Sonobe, Hiroshi Date
The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non-small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB-resistant (VR) lung cancer cells (NCI-H1299 and A549) and examined its transcriptional changes, protein expressions, and activations...
January 10, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29317819/inhibition-of-cancer-cell-migration-with-cus-msio2-peg-nanoparticles-by-repressing-mmp-2-mmp-9-expression
#19
Guoying Deng, Feng Zhou, Zizheng Wu, Fei Zhang, Kerun Niu, Yingjie Kang, Xijian Liu, Qiugen Wang, Yin Wang, Qian Wang
The metastasis of cancer cells is a vital aspect of disease progression and therapy. Although a few nanoparticles (NPs) aimed at controlling metastasis in cancer therapy have been reported, the NPs are normally combined with drugs, yet the direct therapeutic effects of the NPs are not reported. To study the direct influence of NPs on cancer metastasis, the potential suppression capacity of CuS@mSiO2-PEG NPs to tumor cell migration, a kind of typical photothermal NPs, was systemically evaluated in this study...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29315500/long-term-outcome-of-dasatinib-first-line-treatment-in-gastrointestinal-stromal-tumor-a-multicenter-2-stage-phase-2-trial-swiss-group-for-clinical-cancer-research-56-07
#20
Michael Montemurro, Angela Cioffi, Julien Dômont, Piotr Rutkowski, Arnaud D Roth, Roger von Moos, Roman Inauen, Maud Toulmonde, Roger O Burkhard, Claudio Knuesli, Sebastian Bauer, Philippe Cassier, Heike Schwarb, Axel Le Cesne, Dieter Koeberle, Daniela Bärtschi, Daniel Dietrich, Christine Biaggi, John Prior, Serge Leyvraz
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with gastrointestinal stromal tumors (GISTs), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of BCR-ABL, KIT, and SRC family kinases as well as imatinib-resistant cells. In GISTs, response evaluation is routinely done using computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography coupled to CT (FDG-PET/CT) for early response assessment and outcome prediction...
January 9, 2018: Cancer
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