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Serine proteases have been implicated as key drivers and facilitators of lung cancer malignancy, and while these proteins represent straightforward targets for therapeutic inhibitors, identification of optimal points for intervention has been complicated by the complex networks in which these enzymes function. Here we implicate a signaling pathway consisting of PRSS3/mesotrypsin and kallikrein-related peptidase 5 (KLK5) in lung adenocarcinoma malignancy. We show that elevated PRSS3/mesotrypsin expression is prognostic for poor outcome for patients with lung adenocarcinoma, and that genetic or pharmacologic targeting of PRSS3/mesotrypsin reduces lung adenocarcinoma cell invasiveness and proliferation. We further show that genetic targeting of KLK5, a known target of PRSS3/mesotrypsin, phenocopies the effect of PRSS3/mesotrypsin knockdown, and also that elevated expression of KLK5 is similarly prognostic for outcome in lung adenocarcinoma. Finally, we use transcriptional profiling experiments to show that PRSS3/mesotrypsin and KLK5 control a common malignancy-promoting pathway. These experiments implicate a potential PRSS3/mesotrypsin-KLK5 signaling module in lung adenocarcinoma and reveal the potential therapeutic benefit of selectively targeting these pathways.
Pubmed ID: 30755669
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Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsThe DSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (German Collection of Microorganisms and Cell Cultures) is the most comprehensive biological resource center in Europe. With more than 18.000 microorganisms, 1.200 plant viruses, 600 human and animal cell lines, 770 plant cell cultures and more than 7.100 cultures deposited for the purposes of patenting, DSMZ has demonstrated their obligation to serve science for decades. Main functions of DSMZ are: - to collect, maintain and store microorganisms and cell lines, as well as other biological material of relevance for applied biology, biotechnology, microbiology, teaching and other areas of research and general application; - to keep the scientific and industrial community informed on the contents of the collections by the means of catalogs, special lists, databases or electronic media; - to supply scientists and institutions with DSMZ cultures, in accordance with national and international laws such as the Infektionsschutzgesetz (Act dealing with protection against infection), the Genetic Engineering Act, the Foreign Trade Laws, the Convention on Biological Diversity as well as the DSMZ terms of supply; - to function as an internationally recognized collection center for the deposit of microorganisms, cell lines, and other biological material which have been cited in scientific literature or which are used in national or international test procedures (e.g. type strains, reference strains for national and international quality control regulations or susceptibility tests, strains with special properties, such as the production of enzymes, degradation of pollutants, host strains for plasmids, etc.); - to act as an International Depositary Authority (IDA) for the deposit of biological material for patent purposes according to the Budapest Treaty; - to act, in a confidential manner, as a center for the safe deposit of biological material; - to act as an advisory center for the scientific community and to offer teaching and service facilities. The DSMZ collections contain over 26 000 cultures (including 6500 patent deposits) representing more than 16 000 cultures of microorganisms (Archaea, Bacteria, plasmids, phages, yeasts, fungi), 750 plant cell cultures, 600 plant viruses, 700 antisera and 580 human and animal cell lines. Unique subcollections are held in the prokaryotes groups of acidophiles, alkaliphiles, halophiles, methanogens, phototrophs, thermophiles, and sulfate reducers. The research is focused on collection related fields which include: - Taxonomy - Evolution - Phylogeny - Microbial diversity and molecular assessment of diversity - Molecular systematics - Research on pathobiological aspects of leukemia-lymphoma cell lines applying classical and molecular genetics, immunological and cell biological methods * Development of cultivation and preservation methods for biological material * Characterization and identification of biological material
View all literature mentionsProject exploring the spectrum of genomic changes involved in more than 20 types of human cancer that provides a platform for researchers to search, download, and analyze data sets generated. As a pilot project it confirmed that an atlas of changes could be created for specific cancer types. It also showed that a national network of research and technology teams working on distinct but related projects could pool the results of their efforts, create an economy of scale and develop an infrastructure for making the data publicly accessible. Its success committed resources to collect and characterize more than 20 additional tumor types. Components of the TCGA Research Network: * Biospecimen Core Resource (BCR); Tissue samples are carefully cataloged, processed, checked for quality and stored, complete with important medical information about the patient. * Genome Characterization Centers (GCCs); Several technologies will be used to analyze genomic changes involved in cancer. The genomic changes that are identified will be further studied by the Genome Sequencing Centers. * Genome Sequencing Centers (GSCs); High-throughput Genome Sequencing Centers will identify the changes in DNA sequences that are associated with specific types of cancer. * Proteome Characterization Centers (PCCs); The centers, a component of NCI's Clinical Proteomic Tumor Analysis Consortium, will ascertain and analyze the total proteomic content of a subset of TCGA samples. * Data Coordinating Center (DCC); The information that is generated by TCGA will be centrally managed at the DCC and entered into the TCGA Data Portal and Cancer Genomics Hub as it becomes available. Centralization of data facilitates data transfer between the network and the research community, and makes data analysis more efficient. The DCC manages the TCGA Data Portal. * Cancer Genomics Hub (CGHub); Lower level sequence data will be deposited into a secure repository. This database stores cancer genome sequences and alignments. * Genome Data Analysis Centers (GDACs) - Immense amounts of data from array and second-generation sequencing technologies must be integrated across thousands of samples. These centers will provide novel informatics tools to the entire research community to facilitate broader use of TCGA data. TCGA is actively developing a network of collaborators who are able to provide samples that are collected retrospectively (tissues that had already been collected and stored) or prospectively (tissues that will be collected in the future).
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented July 19, 2016. It has been integrated into the National Cancer Informatics Program (NCIP). The National Cancer Institute launched the cancer Biomedical Informatics Grid (caBIG) to create a virtual network of interconnected data, individuals, and organizations that worked together to redefine how cancer research is conducted. caBIG capabilities allowed researchers and clinicians to collaborate more effectively so that complex research questions might be asked and answered faster and more effectively. The mission of caBIG was to develop a truly collaborative information network that accelerated the discovery of new approaches for the detection, diagnosis, treatment, and prevention of cancer, ultimately improving patient outcomes.
View all literature mentionsCommercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsFunctional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)
View all literature mentionsPowerful, accessible statistical tools for fast visualization and analysis of microarrays - expression arrays, miRNA, exon arrays and genomics copy number data.
View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
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