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https://www.readbyqxmd.com/read/28446239/dasatinib%C3%A2-%C3%A2-gefitinib-a-non-platinum-based-combination-with-enhanced-growth-inhibitory-anti-migratory-and-anti-invasive-potency-against-human-ovarian-cancer-cells
#1
Benoît Thibault, Bertrand Jean-Claude
BACKGROUND: Ovarian cancer is the leading cause of death for gynecological cancers and the 6th cause of women cancer death in developed countries. The late stage detection, the peritoneal dissemination and the acquisition of resistance against carboplatin are the main reasons to explain this poor prognosis and strengthen the need of alternative treatments to improve the management of ovarian cancer and/or to sensitize tumors to platinum salts. Epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (Met) and cellular Src kinase (c-Src) are crucial kinases implied in ovarian tumor growth, survival, invasion and resistance to carboplatin...
April 26, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28415760/binding-of-galectin-1-to-integrin-%C3%AE-1-potentiates-drug-resistance-by-promoting-survivin-expression-in-breast-cancer-cells
#2
KeeSoo Nam, Seog-Ho Son, Sunhwa Oh, Donghwan Jeon, Hyungjoo Kim, Dong-Young Noh, Sangmin Kim, Incheol Shin
Galectin-1 is a β-galactoside binding protein secreted by many types of aggressive cancer cells. Although many studies have focused on the role of galectin-1 in cancer progression, relatively little attention has been paid to galectin-1 as an extracellular therapeutic target. To elucidate the molecular mechanisms underlying galectin-1-mediated cancer progression, we established galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA) against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415726/pge2-ep3-src-signaling-induces-egfr-nuclear-translocation-and-growth-through-egfr-ligands-release-in-lung-adenocarcinoma-cells
#3
Lorenzo Bazzani, Sandra Donnini, Federica Finetti, Gerhard Christofori, Marina Ziche
Prostaglandin E2 (PGE2) interacts with tyrosine kinases receptor signaling in both tumor and stromal cells supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, A549 and GLC82, PGE2 promotes nuclear translocation of epidermal growth factor receptor (nEGFR), affects gene expression and induces cell growth. Indeed, cyclin D1, COX-2, iNOS and c-Myc mRNA levels are upregulated following PGE2 treatment. The nuclear localization sequence (NLS) of EGFR as well as its tyrosine kinase activity are required for the effect of PGE2 on nEGFR and downstream signaling activities...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406453/sequence-polymorphism-and-intrinsic-structural-disorder-as-related-to-pathobiological-performance-of-the-helicobacter-pylori-caga-oncoprotein
#4
REVIEW
Hiroko Nishikawa, Masanori Hatakeyama
CagA, an oncogenic virulence factor produced by Helicobacter pylori, is causally associated with the development of gastrointestinal diseases such as chronic gastritis, peptic ulcers, and gastric cancer. Upon delivery into gastric epithelial cells via bacterial type IV secretion, CagA interacts with a number of host proteins through the intrinsically disordered C-terminal tail, which contains two repeatable protein-binding motifs, the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif and the CagA multimerization (CM) motif...
April 13, 2017: Toxins
https://www.readbyqxmd.com/read/28393242/overexpression-of-srcin1-contributes-to-the-growth-and-metastasis-of-colorectal-cancer
#5
Mengnan Zhang, Feng Ma, Ruyi Xie, Yao Wu, Meiyan Wu, Pei Zhang, Ying Peng, Jinjun Zhao, Jing Xiong, Aimin Li, Cheng Kequan, Yali Zhang, Side Liu, Jide Wang, Xueqing Chen
The adaptor protein Srcin1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase (Csk). Srcin1 behaves as a tumour suppressor in breast cancer, but the role of Srcin1 in the development of colorectal cancer (CRC) remains unknown. In the present study, Srcin1 expression in normal tissue was examined by tissue microarray and assessed by immunohistochemistry in 10 patients. In addition, the biological impact of Srcin1 knockdown on CRC cells was investigated in vitro and in vivo...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28381423/integrin-mediated-traction-force-enhances-paxillin-molecular-associations-and-adhesion-dynamics-that-increase-the-invasiveness-of-tumor-cells-into-a-three-dimensional-extracellular-matrix
#6
Armen H Mekhdjian, FuiBoon Kai, Matthew G Rubashkin, Louis S Prahl, Laralynne M Przybyla, Alexandra L McGregor, Emily S Bell, J Matthew Barnes, Christopher C DuFort, Guanqing Ou, Alice C Chang, Luke Cassereau, Steven J Tan, Michael W Pickup, Jonathan N Lakins, Xin Ye, Michael W Davidson, Jan Lammerding, David J Odde, Alexander R Dunn, Valerie M Weaver
Metastasis requires tumor cells to navigate through a stiff stroma, and to squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data showed that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exerted higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model where motors and clutches are both increased...
April 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28376152/co-activation-of-stat3-and-yes-associated-protein-1-yap1-pathway-in-egfr-mutant-nsclc
#7
Imane Chaib, Niki Karachaliou, Sara Pilotto, Jordi Codony Servat, Xueting Cai, Xuefei Li, Ana Drozdowskyj, Carles Codony Servat, Jie Yang, Chunping Hu, Andres Felipe Cardona, Guillermo Lopez Vivanco, Alain Vergnenegre, Jose Miguel Sanchez, Mariano Provencio, Noemi Reguart, Caicun Zhou, Peng Cao, Patrick C Ma, Trever G Bivona, Rafael Rosell
Background: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) and Src-YES-associated protein 1 (YAP1) signaling are dually activated during EGFR TKI treatment to limit therapeutic response. Methods: We used MTT and clonogenic assays, immunoblotting, and quantitative polymerase chain reaction to evaluate the efficacy of EGFR TKI alone and in combination with STAT3 and Src inhibition in three EGFR-mutant NSCLC cell lines...
September 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28356423/phosphorylated-cortactin-recruits-vav2-guanine-nucleotide-exchange-factor-to-activate-rac3-and-promote-invadopodial-function-in-invasive-breast-cancer-cells
#8
Brian J Rosenberg, Hava Gil-Henn, Christopher C Mader, Tiffany Halo, Taofei Yin, John Condeelis, Kazuya Machida, Yi I Wu, Anthony J Koleske
Breast carcinoma cells use specialized, actin-rich protrusions called invadopodia to degrade and invade through the extracellular matrix. Phosphorylation of the actin nucleation promoting factor and actin stabilizing protein cortactin downstream of the EGF receptor-Src-Arg kinase cascade is known to be a critical trigger for invadopodium maturation and subsequent cell invasion in breast cancer cells. The functions of cortactin phosphorylation in this process, however, are not completely understood. We identified the Rho-family guanine nucleotide exchange factor (GEF) Vav2 in a comprehensive screen for human SH2 domains that bind selectively to phosphorylated cortactin...
March 29, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28340615/glucocorticoids-induce-production-of-reactive-oxygen-species-reactive-nitrogen-species-and-dna-damage-through-an-inos-mediated-pathway-in-breast-cancer
#9
Renée L Flaherty, Matthew Owen, Aidan Fagan-Murphy, Haya Intabli, David Healy, Anika Patel, Marcus C Allen, Bhavik A Patel, Melanie S Flint
BACKGROUND: Psychological stress increases the circulating levels of the stress hormones cortisol and norepinephrine (NE). Chronic exposure to elevated stress hormones has been linked to a reduced response to chemotherapy through induction of DNA damage. We hypothesize that stress hormone signalling may induce DNA damage through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and interference in DNA repair processes, promoting tumourigenesis. METHODS: Breast cancer cell lines were incubated with physiological levels of cortisol and NE in the presence and absence of receptor antagonists and inducible nitric oxide synthase (iNOS) inhibitors and DNA damage measured using phosphorylated γ-H2AX...
March 24, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28338646/type-iv-secretion-and-signal-transduction-of-helicobacter-pylori-caga-through-interactions-with-host-cell-receptors
#10
REVIEW
Steffen Backert, Nicole Tegtmeyer
Helicobacter pylori is a highly successful human bacterium, which is exceptionally equipped to persistently inhabit the human stomach. Colonization by this pathogen is associated with gastric disorders ranging from chronic gastritis and peptic ulcers to cancer. Highly virulent H. pylori strains express the well-established adhesins BabA/B, SabA, AlpA/B, OipA, and HopQ, and a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). The adhesins ascertain intimate bacterial contact to gastric epithelial cells, while the T4SS represents an extracellular pilus-like structure for the translocation of the effector protein CagA...
March 24, 2017: Toxins
https://www.readbyqxmd.com/read/28325761/the-aryl-hydrocarbon-receptor-governs-epithelial-cell-invasion-during-oropharyngeal-candidiasis
#11
Norma V Solis, Marc Swidergall, Vincent M Bruno, Sarah L Gaffen, Scott G Filler
Oropharyngeal candidiasis (OPC), caused predominantly by Candida albicans, is a prevalent infection in patients with advanced AIDS, defects in Th17 immunity, and head and neck cancer. A characteristic feature of OPC is fungal invasion of the oral epithelial cells. One mechanism by which C. albicans hyphae can invade oral epithelial cells is by expressing the Als3 and Ssa1 invasins that interact with the epidermal growth factor receptor (EGFR) on epithelial cells and stimulate endocytosis of the organism. However, the signaling pathways that function downstream of EGFR and mediate C...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28286026/clonorchis-sinensis-excretory-secretory-products-promote-the-migration-and-invasion-of-cholangiocarcinoma-cells-by-activating-the-integrin-%C3%AE-4-fak-src-signaling-pathway
#12
Jhang Ho Pak, Qudsia Bashir, In Ki Kim, Sung-Jong Hong, Sejung Maeng, Young Yil Bahk, Tong-Soo Kim
Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion...
March 8, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28280091/dual-inhibition-of-egfr-and-c-src-by-cetuximab-and-dasatinib-combined-with-folfox-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#13
Christine Parseghian, Nila U Parikh, Ji Yuan Wu, Zhi-Qin Jiang, Laura D Henderson, Feng Tian, Brice Pastor, Marc Ychou, Kanwal Raghav, Arvind Dasari, David Fogelman, Anastasia Katsiampoura, David G Menter, Robert A Wolff, Cathy Eng, Michael J Overman, Alain R Thierry, Gary E Gallick, Scott Kopetz
BACKGROUND: Aberrant activation of the intracellular tyrosine kinase Src has been implicated as a mechanism of acquired chemotherapy resistance in metastatic colorectal cancer (mCRC). Here, the oral tyrosine kinase Src inhibitor, dasatinib, was investigated in combination with FOLFOX and cetuximab. METHODS: We performed a phase IB/II study of 77 patients with previously-treated mCRC. Primary objectives were to determine the MTD, dose-limiting-toxicities, pharmacodynamics, and efficacy...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28259897/dual-roles-of-protein-tyrosine-phosphatase-kappa-in-coordinating-angiogenesis-induced-by-pro-angiogenic-factors
#14
Ping-Hui Sun, Gang Chen, Malcolm Mason, Wen G Jiang, Lin Ye
A potential role may be played by receptor-type protein tyrosine phosphatase kappa (PTPRK) in angiogenesis due to its critical function in coordinating intracellular signal transduction from various receptors reliant on tyrosine phosphorylation. In the present study, we investigated the involvement of PTPRK in the cellular functions of vascular endothelial cells (HECV) and its role in angiogenesis using in vitro assays and a PTPRK knockdown vascular endothelial cell model. PTPRK knockdown in HECV cells (HECVPTPRKkd) resulted in a decrease of cell proliferation and cell-matrix adhesion; however, increased cell spreading and motility were seen...
April 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28218905/phosphorylation-mediated-activation-of-ldha-promotes-cancer-cell-invasion-and-tumour-metastasis
#15
L Jin, J Chun, C Pan, G N Alesi, D Li, K R Magliocca, Y Kang, Z G Chen, D M Shin, F R Khuri, J Fan, S Kang
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28215542/hexachlorobenzene-alters-cell-cycle-by-regulating-p27-cyclin-e-cdk2-and-c-src-p27-protein-complexes
#16
C Ventura, M Núñez, V Gaido, C Pontillo, N Miret, A Randi, C Cocca
Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea-induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7...
March 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28208828/ginkgolic-acid-c-17-1-derived-from-ginkgo-biloba-leaves-suppresses-constitutive-and-inducible-stat3-activation-through-induction-of-pten-and-shp-1-tyrosine-phosphatase
#17
Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seung-Hee Ryu, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28192900/biphasic-affinity-chromatographic-approach-for-deep-tyrosine-phosphoproteome-analysis
#18
Zhenzhen Deng, Mingming Dong, Yan Wang, Jing Dong, Shawn S-C Li, Hanfa Zou, Mingliang Ye
Tyrosine phosphorylation (pTyr) is important for normal physiology and implicated in many human diseases, particularly cancer. Identification of pTyr sites is critical to dissecting signaling pathways and understanding disease pathologies. However, compared with serine/threonine phosphorylation (pSer/pThr), the analysis of pTyr at the proteome level is more challenging due to its low abundance. Here, we developed a biphasic affinity chromatographic approach where Src SH2 superbinder was coupled with NeutrAvidin affinity chromatography, for tyrosine phosphoproteome analysis...
February 1, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28184941/combined-effects-of-furanodiene-and-doxorubicin-on-the-migration-and-invasion-of-mda-mb-231-breast-cancer-cells-in-vitro
#19
Zhang-Feng Zhong, Wen Tan, Ke Tian, Hua Yu, Wen-An Qiang, Yi-Tao Wang
Furanodiene is one of the major bioactive components isolated from the natural product of the plant, Curcuma wenyujin Y.H. Chen et C. Ling. Furanodiene has been found to exert anticancer effects in various types of cancer cell lines, as well as exhibit antimetastatic activities. However, the antimetastatic capacity of furanodiene in combination with the common chemotherapy drug doxorubicin has not been investigated. We found that doxorubicin at a non-toxic concentration induced cell migration and cell invasion in highly metastatic breast cancer cells...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28123075/ron-kinase-a-target-for-treatment-of-cancer-induced-bone-destruction-and-osteoporosis
#20
Kelsi Andrade, Jaime Fornetti, Ling Zhao, Scott C Miller, R Lor Randall, Neysi Anderson, Susan E Waltz, Mark McHale, Alana L Welm
Bone destruction occurs in aging and numerous diseases, including osteoporosis and cancer. Many cancer patients have bone osteolysis that is refractory to state-of-the-art treatments, which block osteoclast activity with bisphosphonates or by inhibiting the receptor activator of nuclear factor κB ligand (RANKL) pathway. We previously showed that macrophage-stimulating protein (MSP) signaling, which is elevated in about 40% of breast cancers, promotes osteolytic bone metastasis by activation of the MSP signaling pathway in tumor cells or in the bone microenvironment...
January 25, 2017: Science Translational Medicine
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