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dc.contributor.authorSeto, Danielle N.en_US
dc.contributor.authorKandarian, Susan C.en_US
dc.contributor.authorJackman, Robert W.en_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-02-27T18:13:02Z
dc.date.available2018-02-27T18:13:02Z
dc.date.issued2015-08-07
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/26092726
dc.identifier.citationDanielle N Seto, Susan C Kandarian, Robert W Jackman. 2015. "A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.." J Biol Chem, Volume 290, Issue 32, pp. 19976 - 19986.
dc.identifier.issn1083-351X
dc.identifier.urihttps://hdl.handle.net/2144/27322
dc.description.abstractCachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.en_US
dc.description.sponsorshipR01 AR060217 - NIAMS NIH HHS; UL1 TR000157 - NCATS NIH HHS; UL1-TR000157 - NCATS NIH HHSen_US
dc.description.urihttp://www.jbc.org/content/290/32/19976.full.pdf?sid=936d126d-814b-4f54-961d-0e98caa31314
dc.format.extentp. 19976 - 19986en_US
dc.languageeng
dc.relation.ispartofJ Biol Chem
dc.rights© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.subjectScience & technologyen_US
dc.subjectLife sciences & biomedicineen_US
dc.subjectBiochemistry & molecular biologyen_US
dc.subjectC26 colon carcinomaen_US
dc.subjectJAKen_US
dc.subjectSTAT3en_US
dc.subjectCancer cachexiaen_US
dc.subjectColorectal canceren_US
dc.subjectLeukemia inhibitory factor (LIF)en_US
dc.subjectMuscle atrophyen_US
dc.subjectSkeletal muscleen_US
dc.subjectAdenocarcinomaen_US
dc.subjectAnimalsen_US
dc.subjectAntibodies, neutralizingen_US
dc.subjectCachexiaen_US
dc.subjectCell line, tumoren_US
dc.subjectCell sizeen_US
dc.subjectColonic neoplasmsen_US
dc.subjectCulture media, conditioneden_US
dc.subjectGene expression regulation, neoplasticen_US
dc.subjectGenes, reporteren_US
dc.subjectGreen fluorescent proteinsen_US
dc.subjectJanus kinase 2en_US
dc.subjectLeukemia inhibitory factoren_US
dc.subjectLuciferasesen_US
dc.subjectMaleen_US
dc.subjectMiceen_US
dc.subjectMuscle fibers, skeletalen_US
dc.subjectOncostatin Men_US
dc.subjectPhosphorylationen_US
dc.subjectProtein kinase inhibitorsen_US
dc.subjectSTAT3 transcription factoren_US
dc.subjectSignal transductionen_US
dc.subjectTranscription factor AP-1en_US
dc.subjectBiological sciencesen_US
dc.subjectMedical and health sciencesen_US
dc.subjectChemical sciencesen_US
dc.subjectBiochemistry & molecular biologyen_US
dc.titleA key role for leukemia inhibitory factor in C26 cancer cachexiaen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1074/jbc.M115.638411
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: 12 monthsen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent Collegeen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent College, Health Sciencesen_US
pubs.publication-statusPublisheden_US


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