About: Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events

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About: Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events
Creator	Borlak, Jürgen Gazzana, Giuseppe
topic	covid:d157e36465cbc9b90100fbfaf02c44739d004fbe#this
Source	PMC
abstract	BACKGROUND: Hepatocellular carcinoma (HCC) is on the rise and the sixth most common cancer worldwide. To combat HCC effectively research is directed towards its early detection and the development of targeted therapies. Given the fact that epidermal growth factor (EGF) is an important mitogen for hepatocytes we searched for disease regulated proteins to improve an understanding of the molecular pathogenesis of EGF induced HCC. Disease regulated proteins were studied by 2DE MALDI-TOF/TOF and a transcriptomic approach, by immunohistochemistry and advanced bioinformatics. RESULTS: Mapping of EGF induced liver cancer in a transgenic mouse model identified n = 96 (p < 0.05) significantly regulated proteins of which n = 54 were tumour-specific. To unravel molecular circuits linked to aberrant EGFR signalling diverse computational approaches were employed and this defined n = 7 key nodes using n = 82 disease regulated proteins for network construction. STRING analysis revealed protein-protein interactions of > 70% disease regulated proteins with individual proteins being validated by immunohistochemistry. The disease regulated network proteins were mapped to distinct pathways and bioinformatics provided novel insight into molecular circuits associated with significant changes in either glycolysis and gluconeogenesis, argine and proline metabolism, protein processing in endoplasmic reticulum, Hif- and MAPK signalling, lipoprotein metabolism, platelet activation and hemostatic control as a result of aberrant EGF signalling. The biological significance of the findings was corroborated with gene expression data derived from tumour tissues to evntually define a rationale by which tumours embark on intriguing changes in metabolism that is of utility for an understanding of tumour growth. Moreover, among the EGF tumour specific proteins n = 11 were likewise uniquely expressed in human HCC and for n = 49 proteins regulation in human HCC was confirmed using the publically available Human Protein Atlas depository, therefore demonstrating clinical significance. CONCLUSION: Novel insight into the molecular pathogenesis of EGF induced liver cancer was obtained and among the 37 newly identified proteins several are likely candidates for the development of molecularly targeted therapies and include the nucleoside diphosphate kinase A, bifunctional ATP-dependent dihydroyacetone kinase and phosphatidylethanolamine-binding protein1, the latter being an inhibitor of the Raf-1 kinase. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1312-z) contains supplementary material, which is available to authorized users.
has issue date	2015-02-25(xsd:dateTime)
bibo:doi	10.1186/s12864-015-1312-z
bibo:pmid	25872475
has license	cc-by
sha1sum (hex)	d157e36465cbc9b90100fbfaf02c44739d004fbe
schema:url	https://doi.org/10.1186/s12864-015-1312-z
resource representing a document's title	Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events
has PubMed Central identifier	PMC4357185
has PubMed identifier	25872475
schema:publication	BMC Genomics
resource representing a document's body	covid:d157e36465cbc9b90100fbfaf02c44739d004fbe#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/d157e36465cbc9b90100fbfaf02c44739d004fbe
is schema:about of	named entity 'EGF' named entity 'sixth' named entity 'combat' named entity 'protein kinase' named entity 'hepatocellular carcinomas' named entity 'worldwide' named entity 'transgenic' named entity 'mitochondrial' named entity 'transgenic mice' named entity 'tumour' named entity 'albumin' named entity 'EGF' named entity 'ribosom' named entity 'drug targets' named entity 'MALDI-TOF' named entity 'tubulin' named entity 'AGE' named entity 'serine protease' named entity 'EGFR' named entity 'HCC' named entity 'download 2005' named entity 'FGFR1' named entity 'splice variant' named entity 'HCC' named entity 'fibrosis' named entity 'transgenic' named entity 'EGFR' named entity 'hypoxia' named entity 'disease' named entity 'activated' named entity 'HCC' named entity 'molecular pathogenesis' named entity 'EGF' named entity 'mitogenic' named entity 'liver metastasis' named entity 'liver cancer' named entity 'glutathione' named entity 'molecularly targeted therapies' named entity 'enzyme' named entity 'arginine' named entity 'cellular energy' named entity 'liver' named entity 'HCC' named entity 'superoxide' named entity 'catalyzes' named entity 'metastasis' named entity 'HCC' named entity 'metabolism' named entity 'endoplasmic reticulum' named entity 'KEGG' named entity 'up-regulated' named entity 'MAPK' named entity 'EGF' named entity 'signalling pathway' named entity 'EGFR' named entity 'perfused' named entity 'S100A4' named entity 'tumour growth' named entity 'master regulator' named entity 'biosynthetic pathways' named entity 'transgenic mice' named entity 'HCC' named entity 'platelet activation' named entity 'unfolded protein response' named entity 'catalyzes' named entity 'liver disease' named entity 'protein' named entity 'serum' named entity 'protein' named entity 'down-regulated' named entity 'kininogen' named entity 'HIF-1' named entity 'tumour cells' named entity 'gluconeogenesis' named entity 'protein' named entity 'EGFR' named entity '3-phosphoglycerate' named entity 'autoclaving'

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