Decorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling
dc.creator | Iozzo, Renato V. | |
dc.creator | Buraschi, Simone | |
dc.creator | Genua, Marco | |
dc.creator | Xu, Shi-Qiong | |
dc.creator | Solomides, Charalambos C. | |
dc.creator | Peiper, Stephen C. | |
dc.creator | Gomella, Leonard G. | |
dc.creator | Owens, Rick C. | |
dc.creator | Morrione, Andrea | |
dc.date.accessioned | 2021-11-09T15:40:37Z | |
dc.date.available | 2021-11-09T15:40:37Z | |
dc.date.issued | 2011-10-07 | |
dc.identifier.citation | Alaide 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.issn | 1083-351X | |
dc.identifier.doi | http://dx.doi.org/10.34944/dspace/7078 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12613/7098 | |
dc.description.abstract | We 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.extent | 11 pages | |
dc.language | English | |
dc.language.iso | eng | |
dc.relation.ispartof | Faculty/ Researcher Works | |
dc.relation.haspart | Journal of Biological Chemistry, Vol. 286, No. 40 | |
dc.relation.isreferencedby | Elsevier | |
dc.rights | Attribution CC BY | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Extracellular matrix | |
dc.subject | Growth factors | |
dc.subject | Insulin-like growth factor (IGF) | |
dc.subject | Signal transduction | |
dc.subject | Transformation | |
dc.subject | Bladder cancer | |
dc.subject | Decorin proteoglycan | |
dc.subject | IGF-IR | |
dc.subject | Migration and invasion | |
dc.subject | Signaling | |
dc.title | Decorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling | |
dc.type | Text | |
dc.type.genre | Journal article | |
dc.description.department | Biology | |
dc.relation.doi | https://doi.org/10.1074/jbc.m111.262766 | |
dc.ada.note | For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu | |
dc.description.schoolcollege | Temple University. College of Science and Technology | |
dc.creator.orcid | Morrione|0000-0002-2319-7884 | |
dc.temple.creator | Morrione, Andrea | |
refterms.dateFOA | 2021-11-09T15:40:37Z |