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https://www.readbyqxmd.com/read/29785723/decreased-e-cadherin-in-mcf7-human-breast-cancer-cells-forming-multicellular-spheroids-exposed-to-simulated-microgravity
#1
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/29705335/molecular-mechanisms-of-platelet-activation-and-aggregation-induced-by-breast-cancer-cells
#2
Marta Zarà, Ilaria Canobbio, Caterina Visconte, Jessica Canino, Mauro Torti, Gianni Francesco Guidetti
Tumor cell-induced platelet aggregation represents a critical process both for successful metastatic spread of the tumor and for the development of thrombotic complications in cancer patients. To get further insights into this process, we investigated and compared the molecular mechanisms of platelet aggregation induced by two different breast cancer cell lines (MDA-MB-231 and MCF7) and a colorectal cancer cell line (Caco-2). All the three types of cancer cells were able to induce comparable platelet aggregation, which, however, was observed exclusively in the presence of CaCl2 and autologous plasma...
April 26, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29695515/novel-role-of-prostate-apoptosis-response-4-tumor-suppressor-in-b-cell-chronic-lymphocytic-leukemia
#3
Mary K McKenna, Sunil K Noothi, Sara S Alhakeem, Karine Z Oben, Joseph T Greene, Rajeswaran Mani, Kathryn L Perry, James P Collard, Jacqueline R Rivas, Gerhard Hildebrandt, Roger Fleischman, Eric B Durbin, John C Byrd, Chi Wang, Natarajan Muthusamy, Vivek M Rangnekar, Subbarao Bondada
Prostate apoptosis response-4 (Par-4), a pro-apoptotic tumor suppressor protein, is down regulated in many cancers including renal cell carcinoma, glioblastoma, endometrial and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from the Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1 to S cell cycle transition...
April 25, 2018: Blood
https://www.readbyqxmd.com/read/29694242/endostar-a-modified-endostatin-induces-vascular-normalization-to-improve-chemotherapy-efficacy-through-suppression-of-src-signaling-pathway
#4
Min Yu, Yao Han, Hongyu Zhuo, Shuang Zhang
Pathological angiogenesis can be a significant barrier to effective cancer therapy. Recent evidence suggests that Endostar may induce vascular normalization, thereby improving tumor perfusion and systemic chemotherapy. However, the molecular mechanism by which Endostar makes chemotherapy more effective remains to be fully elucidated. In this study, established 4T1 breast tumor-bearing animals treated with Endostar were evaluated at serial time points for treatment-associated changes in vascular architecture...
April 25, 2018: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29672153/p21-activated-kinase4-in-pancreatic-acini-is-activated-by-gi-hormones-growth-factors-by-novel-signaling-and-is-needed-to-stimulate-secretory-growth-cascades
#5
Irene Ramos-Alvarez, Robert T Jensen
p21-activated kinases(PAKs) are highly conserved serine/threonine protein kinases, which are divided into two groups:Group-I(PAKs1-3) and Group-II(PAKs4-6). In various tissues, Group-II PAKs play important roles in cytoskeletal dynamics, cell growth as well as neoplastic development/progression. However, little is known about Group-II PAKs role in a number of physiological events including their ability to be activated by gastrointestinal(GI) hormones/neurotransmitters/growth-factors(GFs). We used rat pancreatic acini to explore the ability of GI-hormones/neurotransmitters/GFs to activate Group-II-PAKs and the signaling cascades involved...
April 19, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29658958/treatment-with-src-inhibitor-dasatinib-results-in-elevated-metastatic-potential-in-the-4t1-murine-mammary-carcinoma-model
#6
Veronica S Hughes, Dietmar W Siemann
Introduction: The src inhibitor Dasatinib has been widely studied as an anti-metastatic agent. The aims of this study were to examine the effect of Src inhibition on the metastatic potential of the 4T1 murine mammary carcinoma. Context: Src is a non-receptor tyrosine kinase well-known to contribute to the metastatic potential of tumour cells. It does so through alteration of signalling pathways important to metastasis. Elevated levels of Src are common in many cancer types, and have been correlated with tumour progression and poor patient prognosis...
2018: Tumor & microenvironment
https://www.readbyqxmd.com/read/29653289/src-activation-decouples-cell-division-orientation-from-cell-geometry-in-mammalian-cells
#7
Xiaoyan Sun, Hongsheng Qi, Xiuzhen Zhang, Li Li, Jiaping Zhang, Qunli Zeng, George S Laszlo, Bo Wei, Tianhong Li, Jianxin Jiang, Alex Mogilner, Xiaobing Fu, Min Zhao
Orientation of cell division plane plays a crucial role in morphogenesis and regeneration. Misoriented cell division underlies many important diseases, such as cancer. Studies with Drosophila and C. elegance models show that Src, a proto-oncogene tyrosine-protein kinase, is a critical regulator of this aspect of mitosis. However, the role for Src in controlling cell division orientation in mammalian cells is not well understood. Using genetic and pharmacological approaches and two extracellular signals to orient cell division, we demonstrated a critical role for Src...
April 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29615789/metabolic-enzyme-pfkfb4-activates-transcriptional-coactivator-src-3-to-drive-breast-cancer
#8
Subhamoy Dasgupta, Kimal Rajapakshe, Bokai Zhu, Bryan C Nikolai, Ping Yi, Nagireddy Putluri, Jong Min Choi, Sung Y Jung, Cristian Coarfa, Thomas F Westbrook, Xiang H-F Zhang, Charles E Foulds, Sophia Y Tsai, Ming-Jer Tsai, Bert W O'Malley
Alterations in both cell metabolism and transcriptional programs are hallmarks of cancer that sustain rapid proliferation and metastasis1 . However, the mechanisms that control the interaction between metabolic reprogramming and transcriptional regulation remain unclear. Here we show that the metabolic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) regulates transcriptional reprogramming by activating the oncogenic steroid receptor coactivator-3 (SRC-3). We used a kinome-wide RNA interference-based screening method to identify potential kinases that modulate the intrinsic SRC-3 transcriptional response...
April 3, 2018: Nature
https://www.readbyqxmd.com/read/29601121/pai-1-induces-src-inhibitor-resistance-via-ccl5-in-her2-positive-breast-cancer-cells
#9
Hehui Fang, Juan Jin, Doudou Huang, Fang Yang, Xiaoxiang Guan
Tyrosine kinase Src is overexpressed and activated in various tumors, including breast cancer, and is supposed to promote cancer formation and development. Src inhibitors are recently developed and have shown efficacy in breast cancer as single agent or in combination with anti-HER2 antibodies or chemotherapy. Unfortunately, the potency of Src inhibitor is limited by the development of drug resistance. In our study, we established a Src inhibitor saracatinib-resistant breast cancer cell line (SKBR-3/SI) for the first time and by evaluating mRNA expression profile, we first found that plasminogen activator inhibitor-1 (PAI-1) was upregulated in saracatinib-resistant cells compared to the parent cells...
March 30, 2018: Cancer Science
https://www.readbyqxmd.com/read/29531159/acetylation-within-the-n-and-c-terminal-domains-of-src-regulate-distinct-roles-of-stat3-mediated-tumorigenesis
#10
Chao Huang, Zhe Zhang, Lihan Chen, Hank W Lee, Marina K Ayrapetov, Ting C Zhao, Yimei Hao, Jinsong Gao, Chunzhang Yang, Gautam U Mehta, Zhengping Zhuang, Xiaoren Zhang, Guohong Hu, Y Eugene Chin
Post-translational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions: myristoylation of G2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylated an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane...
March 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29524521/decrease-in-paracellular-permeability-and-chemosensitivity-to-doxorubicin-by-claudin-1-in-spheroid-culture-models-of-human-lung-adenocarcinoma-a549-cells
#11
Risa Akizuki, Ryohei Maruhashi, Hiroaki Eguchi, Kazuki Kitabatake, Mitsutoshi Tsukimoto, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Chemotherapy resistance is a major problem in the treatment of cancer, but the underlying mechanisms are not fully understood. We found that the expression levels of claudin-1 (CLDN1) and 3, tight junctional proteins, are upregulated in cisplatin (CDDP)-resistant human lung adenocarcinoma A549 (A549R) cells. A549R cells showed cross-resistance to doxorubicin (DXR). Here, the expression mechanism and function of CLDN1 and 3 were examined. CLDN1 and 3 were mainly localized at tight junctions concomitant with zonula occludens (ZO)-1, a scaffolding protein, in A549 and A549R cells...
May 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29511352/regulation-of-inside-out-%C3%AE-1-integrin-activation-by-cdcp1
#12
Sara G Pollan, Fangjin Huang, Jamie M Sperger, Joshua M Lang, Colm Morrissey, Anne E Cress, C Y Chu, Neil A Bhowmick, Sungyong You, Michael R Freeman, Danislav S Spassov, Mark M Moasser, William G Carter, Shakti Ranjan Satapathy, Kavita Shah, Beatrice S Knudsen
Tumor metastasis depends on the dynamic regulation of cell adhesion through β1-integrin. The Cub-Domain Containing Protein-1, CDCP1, is a transmembrane glycoprotein which regulates cell adhesion. Overexpression and loss of CDCP1 have been observed in the same cancer types to promote metastatic progression. Here, we demonstrate reduced CDCP1 expression in high-grade, primary prostate cancers, circulating tumor cells and tumor metastases of patients with castrate-resistant prostate cancer. CDCP1 is expressed in epithelial and not mesenchymal cells, and its cell surface and mRNA expression declines upon stimulation with TGFβ1 and epithelial-to-mesenchymal transition...
March 7, 2018: Oncogene
https://www.readbyqxmd.com/read/29487290/src-mediated-regulation-of-the-pi3k-pathway-in-advanced-papillary-and-anaplastic-thyroid-cancer
#13
Thomas C Beadnell, Kelsey W Nassar, Madison M Rose, Erin G Clark, Brian P Danysh, Marie-Claude Hofmann, Nikita Pozdeyev, Rebecca E Schweppe
Advanced stages of papillary and anaplastic thyroid cancer continue to be plagued by a dismal prognosis, which is a result of limited effective therapies for these cancers. Due to the high proportion of thyroid cancers harboring mutations in the MAPK pathway, the MAPK pathway has become a focal point for therapeutic intervention in thyroid cancer. Unfortunately, unlike melanoma, a similar responsiveness to MAPK pathway inhibition has yet to be observed in thyroid cancer patients. To address this issue, we have focused on targeting the non-receptor tyrosine kinase, Src, and we and others have demonstrated that targeting Src results in inhibition of growth, invasion, and migration both in vitro and in vivo, which can be enhanced through the combined inhibition of Src and the MAPK pathway...
February 28, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29485707/overexpression-of-tpl2-is-linked-to-imatinib-resistance-and-activation-of-mek-erk-and-nf-%C3%AE%C2%BAb-pathways-in-a-model-of-chronic-myeloid-leukemia
#14
Anna Chorzalska, Nagib Ahsan, R Shyama Prasad Rao, Karim Roder, Xiaoqing Yu, John Morgan, Alexander Tepper, Steven Hines, Peng Zhang, Diana O Treaba, Ting C Zhao, Adam J Olszewski, John L Reagan, Olin Liang, Philip A Gruppuso, Patrycja M Dubielecka
The introduction of tyrosine kinase inhibitors (TKI) has transformed chronic myeloid leukemia (CML) into a chronic disease with long-term survival exceeding 85%. However, resistance of CML stem cells to TKI may contribute to the 50% relapse rate observed after TKI discontinuation in molecular remission. We previously described a model of resistance to imatinib mesylate (IM), in which K562 cells cultured in high concentrations of imatinib mesylate showed reduced Bcr-Abl1 protein and activity levels while maintaining proliferative potential...
May 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29467938/smad4-independent-activation-of-tgf-%C3%AE-signaling-by-muc1-in-a-human-pancreatic-cancer-cell-line
#15
Priyanka Grover, Sritama Nath, Monica D Nye, Ru Zhou, Mohammad Ahmad, Pinku Mukherjee
Pancreatic Ductal Adenocarcinoma (PDA) has a mortality rate that nearly matches its incidence rate. Transforming Growth Factor Beta (TGF-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. There is limited knowledge of how TGF-β function switches during tumorigenesis. Mucin 1 (MUC1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of PDA cases and is associated with poor prognosis. In PDA, MUC1 promotes tumor progression and metastasis via signaling through its cytoplasmic tail (MUC1-CT) and interacting with other oncogenic signaling molecules...
January 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29455668/function-of-the-c-met-receptor-tyrosine-kinase-in-carcinogenesis-and-associated-therapeutic-opportunities
#16
REVIEW
Yazhuo Zhang, Mengfang Xia, Ke Jin, Shufei Wang, Hang Wei, Chunmei Fan, Yingfen Wu, Xiaoling Li, Xiayu Li, Guiyuan Li, Zhaoyang Zeng, Wei Xiong
c-Met is a receptor tyrosine kinase belonging to the MET (MNNG HOS transforming gene) family, and is expressed on the surfaces of various cells. Hepatocyte growth factor (HGF) is the ligand for this receptor. The binding of HGF to c-Met initiates a series of intracellular signals that mediate embryogenesis and wound healing in normal cells. However, in cancer cells, aberrant HGF/c-Met axis activation, which is closely related to c-Met gene mutations, overexpression, and amplification, promotes tumor development and progression by stimulating the PI3K/AKT, Ras/MAPK, JAK/STAT, SRC, Wnt/β-catenin, and other signaling pathways...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29407963/identification-of-novel-n-1-2-aryl-1-3-thiazolidin-4-one-n-3-aryl-ureas-showing-potent-multi-tyrosine-kinase-inhibitory-activities
#17
Baohui Qi, Ying Yang, Huan He, Xupeng Yue, Yuting Zhou, Xing Zhou, Yuying Chen, Min Liu, Anmian Zhang, Fachang Wei
A total of 29 novel compounds bearing N1 -(2-aryl-1, 3-thiazolidin-4-one)-N3 -aryl ureas were designed, synthesized and evaluated for their biological activities. The structure-activity relationships (SARs) and binding modes of this series of compounds were clarified together. Compound 29b was identified possessing high potency against multi-tyrosine kinases including Ron, c-Met, c-Kit, KDR, Src and IGF-1R, etc. In vitro antiproliferation and cytotoxicity of compound 29b against A549 cancer cell line were confirmed by IncuCyte live-cell imaging...
February 25, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29391601/the-oncogenic-tyrosine-kinase-lyn-impairs-the-pro-apoptotic-function-of-bim
#18
Lazaro E Aira, Elodie Villa, Pascal Colosetti, Parvati Gamas, Laurie Signetti, Sandrine Obba, Emma Proics, Fabien Gautier, Béatrice Bailly-Maitre, Arnaud Jacquel, Guillaume Robert, Frédéric Luciano, Philippe P Juin, Jean-Ehrland Ricci, Patrick Auberger, Sandrine Marchetti
Phosphorylation of Ser/Thr residues is a well-established modulating mechanism of the pro-apoptotic function of the BH3-only protein Bim. However, nothing is known about the putative tyrosine phosphorylation of this Bcl-2 family member and its potential impact on Bim function and subsequent Bax/Bak-mediated cytochrome c release and apoptosis. As we have previously shown that the tyrosine kinase Lyn could behave as an anti-apoptotic molecule, we investigated whether this Src family member could directly regulate the pro-apoptotic function of Bim...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29358273/ciap1-2-traf2-shp-1-src-myd88-complex-regulates-lipopolysaccharide-induced-il-27-production-through-nf-%C3%AE%C2%BAb-activation-in-human-macrophages
#19
Aurelia Busca, Yulia Konarski, Niranjala Gajanayaka, Shifawn O'Hara, Jonathan Angel, Maya Kozlowski, Ashok Kumar
The inhibitors of apoptosis (IAP) proteins, initially described in the context of apoptosis regulation as promoting cell survival, have recently emerged as key regulators of innate immune signaling. As a result, downregulation of IAP via Smac mimetics (SMM) has both survival and immunoregulatory effects. IAPs modulate cytokine production in murine models either as a single agent or in response to LPS. However, the role of SMM and the involvement of IAPs in primary human cells and in particular macrophages with respect to cytokine production and innate immune responses remain largely unknown...
March 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29340103/anti-neoplastic-drugs-increase-caveolin-1-dependent-migration-invasion-and-metastasis-of-cancer-cells
#20
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
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