@article {29980,
	title = {IGF-IR cooperates with ERalpha to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules},
	journal = {Sci Rep},
	volume = {7},
	year = {2017},
	note = {Afratis, Nikolaos ABouris, PanagiotisSkandalis, Spyros SMulthaupt, Hinke ACouchman, John RTheocharis, Achilleas DKaramanos, Nikos KengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2017/01/13Sci Rep. 2017 Jan 12;7:40138. doi: 10.1038/srep40138.},
	month = {Jan 12},
	pages = {40138},
	edition = {20170112},
	abstract = {IGF-IR is highly associated with the behaviour of breast cancer cells. In ERalpha-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERalpha-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERalpha-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERalpha signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies.},
	keywords = {*Cell Movement, Breast Neoplasms/*pathology, Cell Proliferation, Estrogen Receptor alpha/*metabolism, Extracellular Matrix/metabolism, Humans, MCF-7 Cells, Receptor, IGF Type 1/*metabolism, signal transduction},
	isbn = {2045-2322 (Electronic)2045-2322 (Linking)},
	author = {Afratis, N. A. and Bouris, P. and Skandalis, S. S. and Multhaupt, H. A. and Couchman, J. R. and Theocharis, A. D. and Karamanos, N. K.}
}
