Networks inferred from biochemical data reveal profound differences in toll-like receptor and inflammatory signaling between normal and transformed hepatocytes

Alexopoulos, LG; Saez-Rodriguez, J; Cosgrove, BD; Lauffenburger, DA; Sorger, PK

dc.contributor.author	Alexopoulos, LG	en
dc.contributor.author	Saez-Rodriguez, J	en
dc.contributor.author	Cosgrove, BD	en
dc.contributor.author	Lauffenburger, DA	en
dc.contributor.author	Sorger, PK	en
dc.date.accessioned	2014-03-01T01:33:51Z
dc.date.available	2014-03-01T01:33:51Z
dc.date.issued	2010	en
dc.identifier.issn	15359476	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/20609
dc.subject	Network Inference	en
dc.subject	Toll Like Receptor	en
dc.subject.other	chemokine	en
dc.subject.other	cyclic AMP responsive element binding protein	en
dc.subject.other	cytokine	en
dc.subject.other	gamma interferon	en
dc.subject.other	glycogen synthase kinase 3	en
dc.subject.other	heat shock protein 27	en
dc.subject.other	I kappa B	en
dc.subject.other	immunoglobulin enhancer binding protein	en
dc.subject.other	insulin receptor substrate 1	en
dc.subject.other	interleukin 1alpha	en
dc.subject.other	interleukin 6	en
dc.subject.other	mitogen activated protein kinase 1	en
dc.subject.other	mitogen activated protein kinase 3	en
dc.subject.other	mitogen activated protein kinase kinase 1	en
dc.subject.other	mitogen activated protein kinase p38	en
dc.subject.other	protein kinase B	en
dc.subject.other	protein p53	en
dc.subject.other	somatomedin C	en
dc.subject.other	STAT3 protein	en
dc.subject.other	STAT6 protein	en
dc.subject.other	stress activated protein kinase	en
dc.subject.other	toll like receptor	en
dc.subject.other	tumor necrosis factor alpha	en
dc.subject.other	article	en
dc.subject.other	cancer cell culture	en
dc.subject.other	cell proliferation	en
dc.subject.other	cell transformation	en
dc.subject.other	cell type	en
dc.subject.other	controlled study	en
dc.subject.other	cytokine release	en
dc.subject.other	down regulation	en
dc.subject.other	human	en
dc.subject.other	human cell	en
dc.subject.other	immune response	en
dc.subject.other	immunocompetent cell	en
dc.subject.other	inflammation	en
dc.subject.other	innate immunity	en
dc.subject.other	liver cell	en
dc.subject.other	priority journal	en
dc.subject.other	proteomics	en
dc.subject.other	signal transduction	en
dc.subject.other	Cell Line, Transformed	en
dc.subject.other	Hepatocytes	en
dc.subject.other	Humans	en
dc.subject.other	Inflammation	en
dc.subject.other	Ligands	en
dc.subject.other	NF-kappa B	en
dc.subject.other	Signal Transduction	en
dc.subject.other	Toll-Like Receptors	en
dc.title	Networks inferred from biochemical data reveal profound differences in toll-like receptor and inflammatory signaling between normal and transformed hepatocytes	en
heal.type	journalArticle	en
heal.identifier.primary	10.1074/mcp.M110.000406	en
heal.identifier.secondary	http://dx.doi.org/10.1074/mcp.M110.000406	en
heal.publicationDate	2010	en
heal.abstract	Systematic study of cell signaling networks increasingly involves high throughput proteomics, transcriptional profiling, and automated literature mining with the aim of assembling large scale interaction networks. In contrast, functional analysis of cell signaling usually focuses on a much smaller sets of proteins and eschews computation but focuses directly on cellular responses to environment and perturbation. We sought to combine these two traditions by collecting cell response measures on a reasonably large scale and then attempting to infer differences in network topology between two cell types. Human hepatocytes and hepatocellular carcinoma cell lines were exposed to inducers of inflammation, innate immunity, and proliferation in the presence and absence of small molecule drugs, and multiplex biochemical measurement was then performed on intra- and extracellular signaling molecules. We uncovered major differences between primary and transformed hepatocytes with respect to the engagement of toll-like receptor and NF-κB-dependent secretion of chemokines and cytokines that prime and attract immune cells. Overall, our results serve as a proof of principle for an approach to network analysis that is systematic, comparative, and biochemically focused. More specifically, our data support the hypothesis that hepatocellular carcinoma cells down-regulate normal inflammatory and immune responses to avoid immune editing. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.	en
heal.journalName	Molecular and Cellular Proteomics	en
dc.identifier.doi	10.1074/mcp.M110.000406	en
dc.identifier.volume	9	en
dc.identifier.issue	9	en
dc.identifier.spage	1849	en
dc.identifier.epage	1865	en