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dc.creatorMata, Roberta
dc.creatorPalladino, Chiara
dc.creatorNicolosi, Maria Luisa
dc.creatorLo Presti, Anna Rita
dc.creatorMalaguarnera, Roberta
dc.creatorRagusa, Marco
dc.creatorSciortino, Daniela
dc.creatorMorrione, Andrea
dc.creatorVella, Veronica
dc.creatorBelfiore, Antonino
dc.identifier.citationMatà R., Palladino C., Nicolosi M. Luisa, Presti A. Rita Lo, Malaguarnera R., Ragusa M., Sciortino D., Morrione A., Maggiolini M., Vella V., Belfiore A. IGF-I induces upregulation of DDR1 collagen receptor in breast cancer cells by suppressing MIR-199a-5p through the PI3K/AKT pathway. Oncotarget. 2016; 7: 7683-7700. Retrieved from
dc.description.abstractDiscoidin Domain Receptor 1 (DDR1) is a collagen receptor tyrosine-kinase that contributes to epithelial-to-mesenchymal transition and enhances cancer progression. Our previous data indicate that, in breast cancer cells, DDR1 interacts with IGF-1R and positively modulates IGF-1R expression and biological responses, suggesting that the DDR1-IGF-IR cross-talk may play an important role in cancer. In this study, we set out to evaluate whether IGF-I stimulation may affect DDR1 expression. Indeed, in breast cancer cells (MCF-7 and MDA-MB-231) IGF-I induced significant increase of DDR1 protein expression, in a time and dose dependent manner. However, we did not observe parallel changes in DDR1 mRNA. DDR1 upregulation required the activation of the PI3K/AKT pathway while the ERK1/2, the p70/mTOR and the PKC pathways were not involved. Moreover, we observed that DDR1 protein upregulation was induced by translational mechanisms involving miR-199a-5p suppression through PI3K/AKT activation. This effect was confirmed by both IGF-II produced by cancer-associated fibroblasts from human breast cancer and by stable transfection of breast cancer cells with a human IGF-II expression construct. Transfection with a constitutively active form of AKT was sufficient to decrease miR-199a-5p and upregulate DDR1. Accordingly, IGF-I-induced DDR1 upregulation was inhibited by transfection with pre-miR-199a-5p, which also impaired AKT activation and cell migration and proliferation in response to IGF-I. These results demonstrate that, in breast cancer cells, a novel pathway involving AKT/miR-199a-5p/DDR1 plays a role in modulating IGFs biological responses. Therefore, this signaling pathway may represent an important target for breast cancers with over-activation of the IGF-IR axis.
dc.format.extent18 pages
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartOncotarget, Vol. 7, No. 8
dc.relation.isreferencedbyImpact Journals
dc.rightsAttribution CC BY
dc.subjectInsulin-like growth factor-I receptor
dc.subjectBreast cancer
dc.titleIGF-I induces upregulation of DDR1 collagen receptor in breast cancer cells by suppressing MIR-199a-5p through the PI3K/AKT pathway
dc.type.genreJournal article
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.temple.creatorMorrione, Andrea

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