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dc.creatorIozzo, Renato V.
dc.creatorBuraschi, Simone
dc.creatorGenua, Marco
dc.creatorXu, Shi-Qiong
dc.creatorSolomides, Charalambos C.
dc.creatorPeiper, Stephen C.
dc.creatorGomella, Leonard G.
dc.creatorOwens, Rick C.
dc.creatorMorrione, Andrea
dc.date.accessioned2021-11-09T15:40:37Z
dc.date.available2021-11-09T15:40:37Z
dc.date.issued2011-10-07
dc.identifier.citationAlaide Morcavallo, Marco Genua, Angela Palummo, Emilia Kletvikova, Jiri Jiracek, Andrzej M. Brzozowski, Renato V. Iozzo, Antonino Belfiore, Andrea Morrione, Insulin and Insulin-like Growth Factor II Differentially Regulate Endocytic Sorting and Stability of Insulin Receptor Isoform A*, Journal of Biological Chemistry, Volume 287, Issue 14, 2012, Pages 11422-11436, ISSN 0021-9258, https://doi.org/10.1074/jbc.M111.252478.
dc.identifier.issn1083-351X
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/7078
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7098
dc.description.abstractWe have recently discovered that the insulin-like growth factor receptor I (IGF-IR) is up-regulated in human invasive bladder cancer and promotes migration and invasion of transformed urothelial cells. The proteoglycan decorin, a key component of the tumor stroma, can positively regulate the IGF-IR system in normal cells. However, there are no available data on the role of decorin in modulating IGF-IR activity in transformed cells or in tumor models. Here we show that the expression of decorin inversely correlated with IGF-IR expression in low and high grade bladder cancers (n = 20 each). Decorin bound with high affinity IGF-IR and IGF-I at distinct sites and negatively regulated IGF-IR activity in urothelial cancer cells. Nanomolar concentrations of decorin promoted down-regulation of IRS-1, one of the critical proteins of the IGF-IR pathway, and attenuated IGF-I-dependent activation of Akt and MAPK. This led to decorin-evoked inhibition of migration and invasion upon IGF-I stimulation. Notably, decorin did not cause down-regulation of the IGF-IR in bladder, breast, and squamous carcinoma cells. This indicates that decorin action on the IGF-IR differs from its known activity on other receptor tyrosine kinases such as the EGF receptor and Met. Our results provide a novel mechanism for decorin in negatively modulating both IGF-I and its receptor. Thus, decorin loss may contribute to increased IGF-IR activity in the progression of bladder cancer and perhaps other forms of cancer where IGF-IR plays a role.
dc.format.extent11 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartJournal of Biological Chemistry, Vol. 286, No. 40
dc.relation.isreferencedbyElsevier
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectExtracellular matrix
dc.subjectGrowth factors
dc.subjectInsulin-like growth factor (IGF)
dc.subjectSignal transduction
dc.subjectTransformation
dc.subjectBladder cancer
dc.subjectDecorin proteoglycan
dc.subjectIGF-IR
dc.subjectMigration and invasion
dc.subjectSignaling
dc.titleDecorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling
dc.typeText
dc.type.genreJournal article
dc.description.departmentBiology
dc.relation.doihttps://doi.org/10.1074/jbc.m111.262766
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.creator.orcidMorrione|0000-0002-2319-7884
dc.temple.creatorMorrione, Andrea
refterms.dateFOA2021-11-09T15:40:37Z


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