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https://www.readbyqxmd.com/read/29792386/disparate-effects-of-shb-gene-deficiency-on-disease-characteristics-in-murine-models-of-myeloid-b-cell-and-t-cell-leukemia
#1
Maria Jamalpour, Xiujuan Li, Karin Gustafsson, Jeffrey W Tyner, Michael Welsh
The Src homology-2 domain protein B is an adaptor protein operating downstream of tyrosine kinases. The Shb gene knockout has been found to accelerate p210 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced leukemia. In human myeloid leukemia were tumors with high Src homology-2 domain protein B mRNA content, tumors were, however, associated with decreased latency and myeloid leukemia exhibiting immune cell characteristics. Thus, the aim of this study was to investigate the effects of Shb knockout on the development of leukemia in three additional models, that is, colony stimulating factor 3 receptor-T618I-induced neutrophilic leukemia, p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced B-cell leukemia, and G12D-Kras-induced T-cell leukemia/thymic lymphoma...
April 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29790812/-express-nav1-7-is-phosphorylated-by-fyn-tyrosine-kinase-which-modulates-channel-expression-and-gating-in-a-cell-type-dependent-manner
#2
Yangyang Li, Tengteng Zhu, Huan Yang, Sulayman Dib-Hajj, Stephen Waxman, Ye Yu, Tian-Le Xu, Xiaoyang Cheng
Voltage-gated sodium channel Nav1.7 is a key molecule in nociception, and its dysfunction has been associated with various pain disorders. Here, we investigated the regulation of Nav1.7 biophysical properties by Fyn, a Src family tyrosine kinase. Nav1.7 was coexpressed with either constitutively active (FynCA) or dominant negative (FynDN) variants of Fyn kinase. FynCA elevated protein expression and tyrosine phosphorylation of Nav1.7 channels. Site-directed mutagenesis analysis identified two tyrosine residues (Y1470 and Y1471) located within the Nav1...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29788096/pnaktide-ameliorates-renal-interstitial-fibrosis-through-inhibition-of-sodium-potassium-adenosine-triphosphatase-mediated-signaling-pathways-in-unilateral-ureteral-obstruction-mice
#3
Xi Cheng, Yi Song, Yu Wang
Background: Sodium-potassium adenosine triphosphatase (Na/K-ATPase) has been shown to regulate Src activity by combining with Src to keep it in an inactive form. We previously reported that Na/K-ATPase was downregulated in unilateral ureteral obstruction (UUO) animals. In this study, we examined whether inhibition of Na/K-ATPase-mediated Src signaling pathways ameliorated renal interstitial fibrosis induced by UUO. Methods: UUO was performed on male C57BL/6J mice...
May 17, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29787750/erybraedin-a-is-a-potential-src-inhibitor-that-blocks-the-adhesion-and-viability-of-non-small-cell-lung-cancer-cells
#4
Hye-Young Min, Yujin Jung, Kwan Hee Park, Won Keun Oh, Ho-Young Lee
The adhesion of cancer cells to the extracellular matrix (ECM) is crucial for cell proliferation, survival, and metastasis. Thus, it is necessary to inhibit cell-ECM adhesion by blocking the activation of the associated signaling to control cancer. Here, we identify erybraedin A (EBA) as a potential Src inhibitor that blocks cell adhesion and viability in non-small-cell lung cancer (NSCLC). EBA significantly inhibited the adhesion of NSCLC cells to fibronectin. EBA also markedly inhibited the activation of Src and its downstream targets, including FAK and Akt...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29785723/decreased-e-cadherin-in-mcf7-human-breast-cancer-cells-forming-multicellular-spheroids-exposed-to-simulated-microgravity
#5
Jayashree Sahana, Mohamed Zakaria Nassef, Markus Wehland, Sascha Kopp, Marcus Krüger, Thomas J Corydon, Manfred Infanger, Johann Bauer, Daniela Grimm
MCF7 human breast cancer cells were cultured under normal gravity (1g) and on a random positioning machine (RPM) preventing sedimentation. After two weeks, adherent 1g-control and adherent RPM cells (AD) as well as multicellular spheroids (MCS) were harvested. AD and MCS had been exposed to the RPM in the same culture flask. In a subsequent proteome analysis, the majority of the proteins detected showed similar label-free quantification scores (LFQ) in each of the respective subpopulations, but in both AD or MCS cultures, proteins were also found whose LFQs deviated at least twofold from their counterparts in the 1g-control cells...
May 21, 2018: Proteomics
https://www.readbyqxmd.com/read/29782351/role-of-lkb1-in-migration-and-invasion-of-cr-vi-transformed-human-bronchial-epithelial-beas-2b-cells
#6
Jian Lu, Zhongping Zhou, Miaomiao Tang, Haijun Shen, Yi Liu, Jin Wang, Yewen Jiang, Yifan Chen, Zhanao Wu
Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epithelial cells. The mechanism underlying its carcinogenicity is unclear in terms of how it facilitates metastases. Cr(VI) compounds are reported to briefly promote cell migration in a concentration-dependent manner and oncogene liver kinase B1 (LKB1) was reduced in Cr(VI)-transformed cells. Overexpression of LKB1 in Beas-2B-Cr [Cr(VI) malignantly transformed Beas-2B cells] suppressed cell migration and invasion and inactivated FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, which contribute to cell migration and invasion...
May 18, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29780898/sumoylation-and-phosphorylation-cross-talk-in-hepatocellular-carcinoma
#7
REVIEW
Maria Lauda Tomasi, Komal Ramani
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. The large spectrum of protein post-translational modification (PTM) includes numerous critical signaling events that occur during neoplastic transformation. PTMs occur to nearly all proteins and increase the functional diversity of proteins. We have reviewed the role of two major PTMs, SUMOylation and phosphorylation, in the altered signaling of key players in HCC...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29776413/the-cxcr4-antagonist-plerixafor-amd3100-promotes-proliferation-of-ewing-sarcoma-cell-lines-in-vitro-and-activates-receptor-tyrosine-kinase-signaling
#8
Philipp Berning, Christiane Schaefer, Dagmar Clemens, Eberhard Korsching, Uta Dirksen, Jenny Potratz
BACKGROUND: The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. METHODS: We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro...
May 18, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#9
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773593/safety-and-efficacy-of-second-line-bosutinib-for-chronic-phase-chronic-myeloid-leukemia-over-a-five-year-period-final-results-of-a-phase-1-2-study
#10
Carlo Gambacorti-Passerini, Jorge E Cortes, Jeff H Lipton, Hagop M Kantarjian, Dong-Wook Kim, Philippe Schafhausen, Rocco Crescenzo, Nathalie Bardy-Bouxin, Mark Shapiro, Kay Noonan, Eric Leip, Liza DeAnnuntis, Tim H Brümmendorf, H Jean Khoury
Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Ph+ chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase 1/2 study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow-up and treatment durations were 54.8 (range, 0.6-96.3) and 25.6 (0.2&-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29765553/acquired-resistance-to-everolimus-in-aromatase-inhibitor-resistant-breast-cancer
#11
Mariko Kimura, Toru Hanamura, Kouki Tsuboi, Yosuke Kaneko, Yuri Yamaguchi, Toshifumi Niwa, Kazutaka Narui, Itaru Endo, Shin-Ichi Hayashi
We previously reported the establishment of several types of long-term estrogen-depleted-resistant (EDR) cell lines from MCF-7 breast cancer cells. Type 1 EDR cells exhibited the best-studied mechanism of aromatase inhibitor (AI) resistance, in which estrogen receptor (ER) expression remained positive and PI3K signaling was upregulated. Type 2 EDR cells showed reduced ER activity and upregulated JNK-related signaling. The mTOR inhibitor everolimus reduced growth in cells similar to Type 1 EDR cells. The present study generated everolimus-resistant (EvR) cells from Types 1 and 2 EDR cells following long-term exposure to everolimus in vitro ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765318/utility-of-a-novel-three-dimensional-and-dynamic-3dd-cell-culture-system-for-pk-pd-studies-evaluation-of-a-triple-combination-therapy-at-overcoming-anti-her2-treatment-resistance-in-breast-cancer
#12
Anusha Ande, Tanaya R Vaidya, Bao N Tran, Michael Vicchiarelli, Ashley N Brown, Sihem Ait-Oudhia
Background: Emergence of Human epidermal growth factor receptor 2 (HER2) therapy resistance in HER2-positive (HER2+) breast cancer (BC) poses a major clinical challenge. Mechanisms of resistance include the over-activation of the PI3K/mTOR and Src pathways. This work aims to investigate a novel combination therapy that employs paclitaxel (PAC), a mitotic inhibitor, with everolimus (EVE), an mTOR inhibitor, and dasatinib (DAS), an Src kinase inhibitor, as a modality to overcome resistance. Methods: Static (two dimensional, 2D) and three-dimensional dynamic (3DD) cell culture studies were conducted using JIMT-1 cells, a HER2+ BC cell line refractory to HER2 therapies...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765299/src-kinase-dependent-rapid-non-genomic-modulation-of-hippocampal-spinogenesis-induced-by-androgen-and-estrogen
#13
Mika Soma, Jonghyuk Kim, Asami Kato, Suguru Kawato
Dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from an axon terminal at the synapse. Memories are stored in synapses which consist of spines and presynapses. Rapid modulations of dendritic spines induced by hippocampal sex steroids, including dihydrotestosterone (DHT), testosterone (T), and estradiol (E2), are essential for synaptic plasticity. Molecular mechanisms underlying the rapid non-genomic modulation through synaptic receptors of androgen (AR) and estrogen (ER) as well as its downstream kinase signaling, however, have not been well understood...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29763550/selective-inhibition-of-the-myeloid-src-family-kinase-fgr-potently-suppresses-aml-cell-growth-in-vitro-and-in-vivo
#14
Mark C Weir, Sherry T Shu, Ravi K Patel, Sabine Hellwig, Li Chen, Li Tan, Nathanael S Gray, Thomas E Smithgall
Acute myelogenous leukemia (AML) is the most common hematologic malignancy in adults, and is often associated with constitutive tyrosine kinase signaling. These pathways involve the non-receptor tyrosine kinases Fes, Syk and the three Src-family kinases expressed in myeloid cells (Fgr, Hck, and Lyn). In this study, we report remarkable anti-AML efficacy of an N-phenylbenzamide kinase inhibitor, TL02-59. This compound potently suppressed the proliferation of bone marrow samples from twenty of twenty-six AML patients, with a striking correlation between inhibitor sensitivity and expression levels of the myeloid Src family kinases Fgr, Hck, and Lyn...
May 15, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29761107/intramolecular-fuzzy-interactions-involving-intrinsically-disordered-domains
#15
REVIEW
Miguel Arbesú, Guillermo Iruela, Héctor Fuentes, João M C Teixeira, Miquel Pons
Structural disorder is an essential ingredient for function in many proteins and protein complexes. Fuzzy complexes describe the many instances where disorder is maintained as a critical element of protein interactions. In this minireview we discuss how intramolecular fuzzy interactions function in signaling complexes. Focussing on the Src family of kinases, we argue that the intrinsically disordered domains that are unique for each of the family members and display a clear fingerprint of long range interactions in Src, might have critical roles as functional sensor or effectors and mediate allosteric communication via fuzzy interactions...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29760707/the-yin-and-yang-of-tyrosine-kinase-inhibition-during-experimental-polymicrobial-sepsis
#16
Cassiano Felippe Gonçalves-de-Albuquerque, Ina Rohwedder, Adriana Ribeiro Silva, Alessandra Silveira Ferreira, Angela R M Kurz, Céline Cougoule, Sarah Klapproth, Tanja Eggersmann, Johnatas D Silva, Gisele Pena de Oliveira, Vera Luiza Capelozzi, Gabriel Gutfilen Schlesinger, Edlaine Rijo Costa, Rita de Cassia Elias Estrela Marins, Attila Mócsai, Isabelle Maridonneau-Parini, Barbara Walzog, Patricia Rieken Macedo Rocco, Markus Sperandio, Hugo Caire de Castro-Faria-Neto
Neutrophils are the first cells of our immune system to arrive at the site of inflammation. They release cytokines, e.g., chemokines, to attract further immune cells, but also actively start to phagocytose and kill pathogens. In the case of sepsis, this tightly regulated host defense mechanism can become uncontrolled and hyperactive resulting in severe organ damage. Currently, no effective therapy is available to fight sepsis; therefore, novel treatment targets that could prevent excessive inflammatory responses are warranted...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29753725/ca-2-signaling-and-src-kinases-controlled-cellular-functions
#17
REVIEW
Estefanía Anguita, Antonio Villalobo
Calcium-mediated signaling and the functionality of Src-family tyrosine kinases (SFKs) are two interconnected processes. Activation of these kinases, which are coupled to a series of receptors, mediates Ca2+ mobilization by regulating Ca2+ channels, and the generated Ca2+ signal in turn exerts control on the kinase activity via calmodulin. In this review, we shall cover the regulation of selected processes where crosstalk between the functionality of SFKs and the Ca2+ signal occurs during the lifespan of the cell, when subjected to different extracellular or intracellular stimuli...
May 10, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29752758/src-type-tyrosine-kinase-p56lck-is-critical-for-thymic-stromal-lymphopoietin-induced-allergic-rhinitis
#18
Sun-Young Nam, Hee-Yun Kim, Na-Ra Han, Phil-Dong Moon, Joong-Saeng Cho, Hyung-Min Kim, Hyun-Ja Jeong
BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analyzed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects...
May 12, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29751129/selective-inhibition-of-src-family-kinases-by-su6656-increases-bone-mass-by-uncoupling-bone-formation-from-resorption-in-mice
#19
Cyril Thouverey, Serge Ferrari, Joseph Caverzasio
Mice deficient in the non-receptor tyrosine kinase Src exhibit high bone mass due to impaired bone resorption and increased bone formation. Although several Src family kinase inhibitors inhibit bone resorption in vivo, they display variable effects on bone formation. SU6656 is a selective Src family kinase inhibitor with weaker activity towards the non-receptor tyrosine kinase Abl and receptor tyrosine kinases which are required for appropriate osteoblast proliferation, differentiation and function. Therefore, we sought to determine whether SU6656 could increase bone mass by inhibiting bone resorption and by stimulating bone formation, and to explore its mechanisms of action...
May 8, 2018: Bone
https://www.readbyqxmd.com/read/29749547/salidroside-inhibits-the-proliferation-and-migration-of-gastric-cancer-cells-via-suppression-of-src%C3%A2-associated-signaling-pathway-activation-and-heat-shock-protein-70-expression
#20
Zhilin Qi, Tuo Tang, Lili Sheng, Yunfei Ma, Yinhua Liu, Liang Yan, Shimei Qi, Liefeng Ling, Yao Zhang
Salidroside, an active ingredient extracted from the Rhodiola rosea plant, has potential anti‑tumor effects. However, the effects of salidroside on gastric cancer cell proliferation and migration remain unclear. In the present study, the inhibitory effects of salidroside on gastric cancer cell proliferation, migration and invasion and the molecular mechanisms underlying these effects were investigated. The human gastric cancer cell line, BGC‑823, was treated with different concentrations of salidroside (200, 400 and 600 µg/ml)...
May 3, 2018: Molecular Medicine Reports
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