<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Afratis, N. A.</style></author><author><style face="normal" font="default" size="100%">Bouris, P.</style></author><author><style face="normal" font="default" size="100%">Skandalis, S. S.</style></author><author><style face="normal" font="default" size="100%">Multhaupt, H. A.</style></author><author><style face="normal" font="default" size="100%">Couchman, J. R.</style></author><author><style face="normal" font="default" size="100%">Theocharis, A. D.</style></author><author><style face="normal" font="default" size="100%">Karamanos, N. K.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">IGF-IR cooperates with ERalpha to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules</style></title><secondary-title><style face="normal" font="default" size="100%">Sci Rep</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">*Cell Movement</style></keyword><keyword><style  face="normal" font="default" size="100%">Breast Neoplasms/*pathology</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Proliferation</style></keyword><keyword><style  face="normal" font="default" size="100%">Estrogen Receptor alpha/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Extracellular Matrix/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">MCF-7 Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor, IGF Type 1/*metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">signal transduction</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">Jan 12</style></date></pub-dates></dates><edition><style face="normal" font="default" size="100%">20170112</style></edition><volume><style face="normal" font="default" size="100%">7</style></volume><pages><style face="normal" font="default" size="100%">40138</style></pages><isbn><style face="normal" font="default" size="100%">2045-2322 (Electronic)2045-2322 (Linking)</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">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.</style></abstract><accession-num><style face="normal" font="default" size="100%">28079144</style></accession-num><notes><style face="normal" font="default" size="100%">Afratis, Nikolaos ABouris, PanagiotisSkandalis, Spyros SMulthaupt, Hinke ACouchman, John RTheocharis, Achilleas DKaramanos, Nikos KengResearch Support, Non-U.S. Gov'tEngland2017/01/13Sci Rep. 2017 Jan 12;7:40138. doi: 10.1038/srep40138.</style></notes><custom2><style face="normal" font="default" size="100%">PMC5228153</style></custom2><auth-address><style face="normal" font="default" size="100%">Biochemistry, Biochemical Analysis &amp;Matrix Pathobiology Res. Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras 26110, Greece.Biotech Research and Innovation Center, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen N, Denmark.</style></auth-address><remote-database-name><style face="normal" font="default" size="100%">Medline</style></remote-database-name><remote-database-provider><style face="normal" font="default" size="100%">NLM</style></remote-database-provider></record></records></xml>