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https://www.readbyqxmd.com/read/28223697/dynamic-regulation-of-gdp-binding-to-g-proteins-revealed-by-magnetic-field-dependent-nmr-relaxation-analyses
#1
Yuki Toyama, Hanaho Kano, Yoko Mase, Mariko Yokogawa, Masanori Osawa, Ichio Shimada
Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28223691/cellular-glycosylation-affects-herceptin-binding-and-sensitivity-of-breast-cancer-cells-to-doxorubicin-and-growth-factors
#2
Diluka Peiris, Alexander F Spector, Hannah Lomax-Browne, Tayebeh Azimi, Bala Ramesh, Marilena Loizidou, Hazel Welch, Miriam V Dwek
Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223314/attenuation-of-epidermal-growth-factor-egf-signaling-by-growth-hormone-gh
#3
Lorena Gonzalez, Johanna Gabriela Miquet, Pablo E Irene, María Eugenia Díaz, Soledad P Rossi, Ana Isabel Sotelo, Mónica B Frungieri, Cristal M Hill, Andrzej Bartke, Daniel Turyn
Transgenic mice overexpressing growth hormone (GH) show increased hepatic protein content of the epidermal growth factor receptor (EGFR), which is broadly associated with cell proliferation and oncogenesis. However, chronically elevated levels of GH result in desensitization of STAT-mediated EGF signal and similar response of Erk1/2 and Akt signaling to EGF compared to normal mice. To ascertain the mechanisms involved in GH attenuation of EGF signaling and the consequences on cell cycle promotion, phosphorylation of signaling mediators was studied at different time points after EGF stimulation, and induction of proteins involved in cell cycle progression was assessed in normal and GH-overexpressing transgenic mice...
February 21, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28222938/the-role-of-mir-17-92-cluster-in-the-expression-of-tumor-suppressor-genes-in-unrestricted-somatic-stem-cells
#4
Rezvan Tavakoli, Saeid Vakilian, Lida Langroudi, Ehsan Arefian, Mehdi Sahmani, Masoud Soleimani, Fatemeh Jamshidi-Adegani
The miR-17-92 cluster consisted of seven miRNAs (mir-17-5p, -17-3p, -18a, -19a, -20a, -19b-1, and -92a-1). Previous studies have shown this cluster has been over-expressed in several cancers. The aim of this study was to evaluate the over-expression impacts of miR-17-92 on stem cells. In the current work, the effect of miR-17-92 cluster which was cloned in Lentiviral vector has been investigated on unrestricted somatic stem cells (USSCs). Tumor suppressor genes (p53, p15, RBL1, SMAD2, SMAD4, and MAPK-1) expression, especially p53, was considerably reduced...
February 17, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28220614/comparative-analysis-of-dna-methylation-patterns-of-equine-sarcoid-and-healthy-skin-samples
#5
E Semik, T Ząbek, A Gurgul, A Fornal, T Szmatoła, K Pawlina, M Wnuk, J Klukowska-Rötzler, C Koch, K Mählmann, M Bugno-Poniewierska
OBJECTIVE: In this study, for the first time we report the genome-wide DNA methylation profile of skin tumour in horses and describe differentially methylated genomic regions (DMRs) with respect to healthy skin. MATERIALS & METHODS: The comparative analysis of DNA methylation patterns detected using Reduced Representation Bisulfite Sequencing (RRBS) technique, allowed identification of 136 regions showing differential methylation between sarcoid and normal skin tissue...
February 21, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28212658/c-met-expression-and-activity-in-urogenital-cancers-novel-aspects-of-signal-transduction-and-medical-implications
#6
REVIEW
Ralf Hass, Susanne Jennek, Yuanyuan Yang, Karlheinz Friedrich
C-Met is a receptor tyrosine kinase with multiple functions throughout embryonic development, organogenesis and wound healing and is expressed in various epithelia. The ligand of c-Met is Hepatocyte Growth Factor (HGF) which is secreted among others by mesenchymal stroma/stem (MSC) cells.Physiological c-Met functions are centred around processes that underly cellular motility and invasive growth. Aberrant c-Met expression and activity is observed in numerous cancers and makes major contributions to cell malignancy...
February 17, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28210393/has-vitamin-d-had-its-time-in-the-sun-for-melanoma
#7
Christopher J Huerter, Adam Vaudreuil, Devendra K Agrawal, Austin Huy Nguyen
Growing evidence suggests a pivotal role for vitamin D in cancers, particularly melanoma. The broad immunologic effects of vitamin D and its signaling axis make for a complex interplay between tumor cells and the immune system. Preclinical evidence suggests vitamin D to have protective effects in melanoma oncogenesis and progression, creating a potential role for vitamin D supplementation in cancer prevention and/or adjuvant therapy. In this commentary, the authors highlight studies of vitamin D in melanoma with clinical implications and call for large clinical trials to definitively determine the role of supplementation in patients to prevent and help treat melanoma...
December 2016: Journal of Clinical and Aesthetic Dermatology
https://www.readbyqxmd.com/read/28209925/the-stress-polarity-pathway-ampk-giv-es-protection-against-metabolic-insults
#8
Pradipta Ghosh
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/28209620/the-histone-methyltransferase-dot1l-promotes-neuroblastoma-by-regulating-gene-transcription
#9
Matthew Wong, Andrew El Tee, Giorgio Milazzo, Jessica L Bell, Rebecca C Poulos, Bernard Atmadibrata, Yuting Sun, Duohui Jing, Nicholas Ho, Dora Ling, Pei Yan Liu, Xu Dong Zhang, Stefan Hüttelmaier, Jason W H Wong, Jenny Wang, Patsie Polly, Giovanni Perini, Christopher J Scarlett, Tao Liu
Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyses H3K79 methylation. Here we show that N-Myc upregulatsd DOT1L mRNA and protein expression by binding to the DOT1L gene promoter. shRNA-mediated depletion of DOT1L reduced mRNA and protein expression of N-Myc target genes ODC1 and E2F2...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209106/gastroesophageal-junction-and-gastroesophageal-junction-carcinoma%C3%A2-a-short-update
#10
REVIEW
K A Ekmektzoglou, P Apostolopoulos, G Samelis, G Alexandrakis
Cancer of the gastroesophageal junction (GEJ), although rare, is now considered a separate entity with a distinct pathophysiological and molecular profile. Although much progress has been made over the past decades in delineating the multiple environmental and genetic pathways involved GEJ carcinoma, the exact molecular mechanisms underlying disease initiation and progression are still poorly understood. This is of paramount importance for the treating physician as the disease bears a poor therapeutic response...
September 2016: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/28207739/overexpression-of-notch-regulated-ankyrin-repeat-protein-is-associated-with-papillary-thyroid-carcinoma-progression
#11
Mingdi Zhang, Yiyu Qin, Bin Zuo, Wei Gong, Shenglai Zhang, Yurong Gong, Zhiwei Quan, Bingfeng Chu
Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28204810/htlv-1-basic-leucine-zipper-factor-downregulates-cyclin%C3%A2-d1-expression-via-interactions-with-nf-%C3%AE%C2%BAb
#12
Yunyun Ma, Bo Zhang, Dong Wang, Lili Qian, Xianmei Song, Xueyin Wang, Chaokuan Yang, Guoqiang Zhao
Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus. It can cause adult T cell leukemia (ATL) and other diseases. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ), which is encoded by the minus-strand of the provirus, is expressed in all cases of ATL and involved in T cell proliferation. However, the exact mechanism underlying its growth-promoting activity is poorly understood. Herein, we demonstrated that HBZ suppressed cyclin D1 expression by inhibiting the nuclear factor (NF)-κB signaling pathway...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28202659/the-short-and-the-long-non-coding-rnas-and-growth-factors-in-cancer-progression
#13
REVIEW
Aldema Sas-Chen, Swati Srivastava, Yosef Yarden
A relatively well-understood multistep process enables mutation-bearing cells to form primary tumours, which later use the circulation system to colonize new locations and form metastases. However, in which way the emerging abundance of different non-coding RNAs supports tumour progression is poorly understood. Here, we review new lines of evidence linking long and short types of non-coding RNAs to signalling pathways activated in the course of cancer progression by growth factors and by the tumour micro-environment...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28196852/inpp4b-and-pten-loss-leads-to-pi-3-4-p2-accumulation-and-inhibition-of-pi3k-in-tnbc
#14
Darien E Reed, Kevan M Shokat
: Triple-negative breast cancer [TNBC, lacks expression of estrogen receptor (ER), progesterone receptor (PR) and amplification of HER2/Neu] remains one of the most aggressive subtypes, affects the youngest patients and still lacks an effective targeted therapy(1,2). Both phosphatidylinositol-3-kinase (PI3K)-α and -β contribute to oncogenesis of solid tumors, including the development of breast cancer(3). Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3,4-bisphosphate (PI-3,4-P2) creating phosphatidylinositol-3-phosphate(4)...
February 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28196522/xpo1-in-b-cell-hematological-malignancies-from-recurrent-somatic-mutations-to-targeted-therapy
#15
REVIEW
Vincent Camus, Hadjer Miloudi, Antoine Taly, Brigitte Sola, Fabrice Jardin
Many recent publications highlight the large role of the pivotal eukaryotic nuclear export protein exportin-1 (XPO1) in the oncogenesis of several malignancies, and there is emerging evidence that XPO1 inhibition is a key target against cancer. The clinical validation of the pharmacological inhibition of XPO1 was recently achieved with the development of the selective inhibitor of nuclear export compounds, displaying an interesting anti-tumor activity in patients with massive pre-treated hematological malignancies...
February 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28194275/inappropriate-costimulation-and-aberrant-dna-methylation-as-therapeutic-targets-in-angioimmunoblastic-t-cell-lymphoma
#16
EDITORIAL
Mathijs Willemsen, Harry C Schouten
Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common subtypes of peripheral T-cell lymphoma. Advances in understanding the mutational landscape of AITL have not resulted in improved prognosis nor consensus regarding optimal first-line and second-line treatment. The recently proposed multistep tumorigenesis model for AITL provides a theoretical framework of AITL oncogenesis. In this model, early mutations in epigenetic modifiers interact with late cooperative mutations to enable malignant transformation...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28183315/pyruvate-kinase-m2-and-the-mitochondrial-atpase-inhibitory-factor-1-provide-novel-biomarkers-of-dermatomyositis-a-metabolic-link-to-oncogenesis
#17
Fulvio Santacatterina, María Sánchez-Aragó, Marc Catalán-García, Glòria Garrabou, Cristina Nuñez de Arenas, Josep M Grau, Francesc Cardellach, José M Cuezva
BACKGROUND: Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. METHODS: A cohort of thirty-two muscle biopsies and forty plasma samples comprising polymyositis (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) and control donors was interrogated with monoclonal antibodies against proteins of energy metabolism using reverse phase protein microarrays (RPPA)...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28182015/mcm7-promotes-cancer-progression-through-cyclin-d1-dependent-signaling-and-serves-as-a-prognostic-marker-for-patients-with-hepatocellular-carcinoma
#18
Kai Qu, Zhixin Wang, Haining Fan, Juan Li, Jie Liu, Pingping Li, Zheyong Liang, Hongli An, Yina Jiang, Qiushi Lin, Xiaoqun Dong, Peijun Liu, Chang Liu
DNA replication is a central procedure of cell proliferation, whereas aberrant DNA replication is indicated to be a driving force of oncogenesis. Minichromosome maintenance complex component 7 (MCM7) plays an essential role in initiating DNA replication. To investigate the potential oncogenic properties and prognostic value of MCM7 in hepatocellular carcinoma (HCC), we conducted immunohistochemistry staining of MCM7 in 153 HCC samples and found that MCM7 high expression level was associated with worse overall survival (OS) of HCC patients...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28182012/loss-of-brg1-induces-crc-cell-senescence-by-regulating-p53-p21-pathway
#19
Guihua Wang, Yinjia Fu, Fuqing Hu, Jinqing Lan, Feng Xu, Xi Yang, Xuelai Luo, Jing Wang, Junbo Hu
Brahma-related gene-1 (BRG1) is the specific ATPase of switch/sucrose nonfermentable chromatin-remodeling complex that is aberrantly expressed or mutated in various cancers. However, the exact role of BRG1 in oncogenesis remains unknown. In this study, we demonstrate that the knockdown (KD) of BRG1 promotes cellular senescence by influencing the SIRT1/p53/p21 signal axis in colorectal cancer (CRC). In particular, we reveal that the expression level of BRG1 is inversely correlated with p21, one of the classic senescence regulators, and is decreased in senescent CRC cells...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28179601/regulation-of-ras-signaling-and-function-by-plasma-membrane-microdomains
#20
Lawrence E Goldfinger, James V Michael
Together H-, N- and KRAS mutations are major contributors to ~30% of all human cancers. Thus, Ras inhibition remains an important anti-cancer strategy. The molecular mechanisms of isotypic Ras oncogenesis are still not completely understood. Monopharmacological therapeutics have not been successful in the clinic. These disappointing outcomes have led to attempts to target elements downstream of Ras, mainly targeting either the Phosphatidylinositol 3-Kinase (PI3K) or Mitogen-Activated Protein Kinase (MAPK) pathways...
February 7, 2017: Bioscience Trends
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