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mapk signalling path

Zhaorui Zhang, Zhixin Liang, Huaidong Li, Chunsun Li, Zhen Yang, Yanqin Li, Danyang She, Lu Cao, Wenjie Wang, Changlin Liu, Liangan Chen
BACKGROUND AND OBJECTIVE: Blast lung injury is a common type of blast injury and has very high mortality. Therefore, research to identify medical therapies for blast injury is important. Perfluorocarbon (PFC) is used to improve gas exchange in diseased lungs and has anti-inflammatory functions in vitro and in vivo. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action. STUDY DESIGN AND METHODS: A549 alveolar epithelial cells exposed to blast waves were treated with and without PFC...
2017: PloS One
Simon J Leedham
The existence and interaction of proliferating and quiescent intestinal stem cells have been debated since their discovery in the 1970s. In this issue of Cell Stem Cell, using murine intestinal organoids, Basak et al. (2017) induce stem cell quiescence by selective inhibition of EGF/MAPK signaling and define culture conditions that direct differentiation to the enteroendocrine lineage.
February 2, 2017: Cell Stem Cell
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
March 2017: Purinergic Signalling
Jessica Segalés, Eusebio Perdiguero, Pura Muñoz-Cánoves
Formation of skeletal muscle fibers (myogenesis) during development and after tissue injury in the adult constitutes an excellent paradigm to investigate the mechanisms whereby environmental cues control gene expression programs in muscle stem cells (satellite cells) by acting on transcriptional and epigenetic effectors. Here we will review the molecular mechanisms implicated in the transition of satellite cells throughout the distinct myogenic stages (i.e., activation from quiescence, proliferation, differentiation, and self-renewal)...
2016: Frontiers in Cell and Developmental Biology
Callie R Merry, Sarah McMahon, Megan E Forrest, Cynthia F Bartels, Alina Saiakhova, Courtney A Bartel, Peter C Scacheri, Cheryl L Thompson, Mark W Jackson, Lyndsay N Harris, Ahmad M Khalil
Approximately, 25-30% of early-stage breast tumors are classified at the molecular level as HER2-positive, which is an aggressive subtype of breast cancer. Amplification of the HER2 gene in these tumors results in a substantial increase in HER2 mRNA levels, and consequently, HER2 protein levels. HER2, a transmembrane receptor tyrosine kinase (RTK), is targeted therapeutically by a monoclonal antibody, trastuzumab (Tz), which has dramatically improved the prognosis of HER2-driven breast cancers. However, ~30% of patients develop resistance to trastuzumab and recur; and nearly all patients with advanced disease develop resistance over time and succumb to the disease...
August 16, 2016: Oncotarget
Simon Rousseau, Guy Martel
Lymphoid neoplasms form a family of cancers affecting B-cells, T-cells, and NK cells. The Toll-Like Receptor (TLR) signaling adapter molecule MYD88 is the most frequently mutated gene in these neoplasms. This signaling adaptor relays signals from TLRs to downstream effector pathways such as the Nuclear Factor kappa B (NFκB) and Mitogen Activated Protein Kinase (MAPK) pathways to regulate innate immune responses. Gain-of-function mutations such as MYD88[L265P] activate downstream signaling pathways in absence of cognate ligands for TLRs, resulting in increased cellular proliferation and survival...
2016: Frontiers in Cell and Developmental Biology
Chen Chen, Hong Shen, Li-Guo Zhang, Jian Liu, Xiao-Ge Cao, An-Liang Yao, Shao-San Kang, Wei-Xing Gao, Hui Han, Feng-Hong Cao, Zhi-Guo Li
Currently, using human prostate cancer (PCa) tissue samples to conduct proteomics research has generated a large amount of data; however, only a very small amount has been thoroughly investigated. In this study, we manually carried out the mining of the full text of proteomics literature that involved comparisons between PCa and normal or benign tissue and identified 41 differentially expressed proteins verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction (PPI) network...
June 2016: International Journal of Molecular Medicine
Miles A Miller, Madeleine J Oudin, Ryan J Sullivan, Stephanie J Wang, Aaron S Meyer, Hyungsoon Im, Dennie T Frederick, Jenny Tadros, Linda G Griffith, Hakho Lee, Ralph Weissleder, Keith T Flaherty, Frank B Gertler, Douglas A Lauffenburger
UNLABELLED: Kinase inhibitor resistance often involves upregulation of poorly understood "bypass" signaling pathways. Here, we show that extracellular proteomic adaptation is one path to bypass signaling and drug resistance. Proteolytic shedding of surface receptors, which can provide negative feedback on signaling activity, is blocked by kinase inhibitor treatment and enhances bypass signaling. In particular, MEK inhibition broadly decreases shedding of multiple receptor tyrosine kinases (RTK), including HER4, MET, and most prominently AXL, an ADAM10 and ADAM17 substrate, thus increasing surface RTK levels and mitogenic signaling...
April 2016: Cancer Discovery
Akiko Nishimura, Katsuyoshi Yamamoto, Masaaki Oyama, Hiroko Kozuka-Hata, Haruo Saito, Kazuo Tatebayashi
In the budding yeast Saccharomyces cerevisiae, osmostress activates the Hog1 mitogen-activated protein kinase (MAPK), which regulates diverse osmoadaptive responses. Hkr1 is a large, highly glycosylated, single-path transmembrane protein that is a putative osmosensor in one of the Hog1 upstream pathways termed the HKR1 subbranch. The extracellular region of Hkr1 contains both a positive and a negative regulatory domain. However, the function of the cytoplasmic domain of Hkr1 (Hkr1-cyto) is unknown. Here, using a mass spectrometric method, we identified a protein, termed Ahk1 (Associated with Hkr1), that binds to Hkr1-cyto...
January 19, 2016: Molecular and Cellular Biology
Li Wang, Jing Li, Hongying Zhao, Jing Hu, Yanyan Ping, Feng Li, Yujia Lan, Chaohan Xu, Yun Xiao, Xia Li
Crosstalk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. How long non-coding RNAs (lncRNAs) participate in the regulation of an abnormal pathway crosstalk in human cancer is largely unknown. Here, we proposed a strategy that integrates mRNA and lncRNA expression profiles for systematic identification of lncRNA-mediated crosstalk among risk pathways in different breast cancer subtypes. We identified 12 to 44 crosstalking pathway pairs mediated by 28 to 49 lncRNAs in four breast cancer subtypes...
March 2016: Molecular BioSystems
Aliakbar Taherian, Thomas A Haas, Abdoulhossein Davoodabadi
BACKGROUND: Breast cancer has been one of the most common types of cancer, as the leading cause of women death in world. Breast cancer has known as a heterogenic disease that the clinical path in different patients would be very different. Since the current classification has not covered the diverse clinical course of breast cancer, lots of efforts has done to find new biological markers. Integrins are hetero dimmer proteins of α and β subunits on cell membrane. After binding to extra cellular matrix (ECM), integrins activate MAPK pathway that regulated different activities like survival, differentiation, migration, immunologic response...
October 2015: Iranian Journal of Cancer Prevention
Ping Ma, Xiao-Yuan Mao, Xiao-Lei Li, Ying Ma, Yuan-Dong Qiao, Zhao-Qian Liu, Hong-Hao Zhou, Yong-Gang Cao
Baicalin is an important active component of the medicinal herb Scutellaria baicalensis Georgi and has shown a variety of pharmacological actions. The present study aimed to evaluate the neuroprotective effects of baicalin against diabetes‑associated cognitive deficits (DACD) in rats and to elucidate the potential molecular mechanisms of action. A rat model of diabetes mellitus was prepared by intraperitoneal injection of streptozotocin. After the successful establishment of the diabetic rat model, baicalin (50, 100 and 200 mg/kg) or vehicle was administrated for seven weeks...
October 2015: Molecular Medicine Reports
Luis Steven Servín-González, Angelica Judith Granados-López, Jesús Adrián López
Tumor cells have developed advantages to acquire hallmarks of cancer like apoptosis resistance, increased proliferation, migration, and invasion through cell signaling pathway misregulation. The sequential activation of genes in a pathway is regulated by miRNAs. Loss or gain of miRNA expression could activate or repress a particular cell axis. It is well known that aberrant miRNA expression is well recognized as an important step in the development of cancer. Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s) or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2), which regulated mitogen-activated protein kinases (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), NOTCH, proteasome-culling rings, and apoptosis cell signaling...
2015: International Journal of Molecular Sciences
Ling Gao, Xiaolong Wang, Xiaofei Wang, Linmei Zhang, Cui Qiang, Su'e Chang, Wenhao Ren, Shaoming Li, Yang Yang, Dongdong Tong, Cheng Chen, Zongfang Li, Tusheng Song, Keqian Zhi, Chen Huang
Insulin-like growth factor (IGF) signaling is involved in oral squamous cell carcinoma (OSCC), but IGF-1 receptor (IGF-1R)-mediated intricate regulatory networks among molecular interactions and signalling path ways in OSCC remain unclear. Here, we found that overexpression of IGF-1R and insulin receptor substrate-2 (IRS-2) was negatively associated with histological differentiation. IGF signaling stimulated OSCC cell growth. Conversely, overexpression of let-7b inhibited proliferation and colony formation and triggered S/G2 cell cycle arrest by targeting IGF-1R and IRS-2 through the Akt pathway...
May 15, 2014: Oncotarget
Sophie Vriz, Silke Reiter, Brigitte Galliot
Recent studies in Drosophila, Hydra, planarians, zebrafish, mice, indicate that cell death can open paths to regeneration in adult animals. Indeed injury can induce cell death, itself triggering regeneration following an immediate instructive mechanism, whereby the dying cells release signals that induce cellular responses over short and/or long-range distances. Cell death can also provoke a sustained derepressing response through the elimination of cells that suppress regeneration in homeostatic conditions...
2014: Current Topics in Developmental Biology
Peng Luo, Ai-hua Zhang, Yun Xiao, Xue-li Pan, Xue-xin Dong, Xiao-xin Huang
OBJECTIVE: To detect the mRNA expression of ERK1, ERK2, JNK1 and P38 gene in mitogen-activated protein kinase(MAPK) path way in the arseniasis patients caused by burning coal. METHODS: 70 arseniasis patients caused by burning coal at Jiaole village XingRen county in December 2006 were selected as case group, and another 30 villagers with similar living habits, matched gender and age, healthy physical condition without history of burning high arsenic coal were selected as control group from 12 km nearby the same village...
September 2013: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Markus Rottmar, Rami Mhanna, Stefanie Guimond-Lischer, Viola Vogel, Marcy Zenobi-Wong, Katharina Maniura-Weber
Chondrocytes rapidly lose their phenotypic expression of collagen II and aggrecan when grown on 2D substrates. It has generally been observed that a fibroblastic morphology with strong actin-myosin contractility inhibits chondrogenesis, whereas chondrogenesis may be promoted by depolymerization of the stress fibers and/or disruption of the physical link between the actin stress fibers and the ECM, as is the case in 3D hydrogels. Here we studied the relationship between the actin-myosin cytoskeleton and expression of chondrogenic markers by culturing fibroblastic chondrocytes in the presence of cytochalasin D and staurosporine...
January 15, 2014: Experimental Cell Research
Joseph A Ludwig, Salah-Eddine Lamhamedi-Cherradi, Ho-Young Lee, Aung Naing, Robert Benjamin
The insulin-like growth factor pathway, regulated by a complex interplay of growth factors, cognate receptors, and binding proteins, is critically important for many of the hallmarks of cancer such as oncogenesis, cell division, growth, and antineoplastic resistance. Naturally, a number of clinical trials have sought to directly abrogate insulin-like growth factor receptor 1 (IGF-1R) function and/or indirectly mitigate its downstream mediators such as mTOR, PI3K, MAPK, and others under the assumption that such therapeutic interventions would provide clinical benefit, demonstrable by impaired tumor growth as well as prolonged progression-free and overall survival for patients...
July 26, 2011: Cancers
Jennifer Yen, Richard M White, David C Wedge, Peter Van Loo, Jeroen de Ridder, Amy Capper, Jennifer Richardson, David Jones, Keiran Raine, Ian R Watson, Chang-Jiun Wu, Jiqiu Cheng, Iñigo Martincorena, Serena Nik-Zainal, Laura Mudie, Yves Moreau, John Marshall, Manasa Ramakrishna, Patrick Tarpey, Adam Shlien, Ian Whitmore, Steve Gamble, Calli Latimer, Erin Langdon, Charles Kaufman, Mike Dovey, Alison Taylor, Andy Menzies, Stuart McLaren, Sarah O'Meara, Adam Butler, Jon Teague, James Lister, Lynda Chin, Peter Campbell, David J Adams, Leonard I Zon, E Elizabeth Patton, Derek L Stemple, P Andy Futreal
BACKGROUND: Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. RESULTS: To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines...
2013: Genome Biology
Sadani N Cooray, Thomas Gobbetti, Trinidad Montero-Melendez, Simon McArthur, Dawn Thompson, Adrian J L Clark, Roderick J Flower, Mauro Perretti
Formyl-peptide receptor type 2 (FPR2), also called ALX (the lipoxin A4 receptor), conveys the proresolving properties of lipoxin A4 and annexin A1 (AnxA1) and the proinflammatory signals elicited by serum amyloid protein A and cathelicidins, among others. We tested here the hypothesis that ALX might exist as homo- or heterodimer with FPR1 or FPR3 (the two other family members) and operate in a ligand-biased fashion. Coimmunoprecipitation and bioluminescence resonance energy transfer assays with transfected HEK293 cells revealed constitutive dimerization of the receptors; significantly, AnxA1, but not serum amyloid protein A, could activate ALX homodimers...
November 5, 2013: Proceedings of the National Academy of Sciences of the United States of America
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