@article { , title = {Survival outcome and EMT suppression mediated by a lectin domain interaction of Endo180 and CD147}, abstract = {Epithelial cell-cell contacts maintain normal glandular tissue homeostasis, and their breakage can trigger epithelial-to-mesenchymal transition (EMT), a fundamental step in the development of metastatic cancer. Despite the ability of C-type lectin domains (CTLD) to modulate cell-cell adhesion, it is not known if they modulate epithelial adhesion in EMT and tumor progression. Here, the multi-CTLD mannose receptor, Endo180 (MRC2/uPARAP), was shown using the Kaplan-Meier analysis to be predictive of survival outcome in men with early prostate cancer. A proteomic screen of novel interaction partners with the fourth CTLD (CTLD4) in Endo180 revealed that its complex with CD147 is indispensable for the stability of three-dimensional acini formed by nontransformed prostate epithelial cells (PEC). Mechanistic study using knockdown of Endo180 or CD147, and treatment with an Endo180 mAb targeting CTLD4 (clone 39.10), or a dominant-negative GST-CTLD4 chimeric protein, induced scattering of PECs associated with internalization of Endo180 into endosomes, loss of E-cadherin (CDH1/ECAD), and unzipping of cell-cell junctions. These findings are the first to demonstrate that a CTLD acts as a suppressor and regulatory switch for EMT; thus, positing that stabilization of Endo180-CD147 complex is a viable therapeutic strategy to improve rates of prostate cancer survival.}, doi = {10.1158/1541-7786.mcr-14-0344-t}, eissn = {1557-3125}, issn = {1541-7786}, issue = {3}, journal = {Molecular cancer research}, pages = {538-547}, publicationstatus = {Published}, publisher = {American Association for Cancer Research}, url = {https://hull-repository.worktribe.com/output/384598}, volume = {13}, keyword = {Health and Health Inequalities, Epithelial-to-mesenchymal transition (EMT)}, year = {2015}, author = {Rodriguez-Teja, Mercedes and Gronau, Julian H. and Minamidate, Ai and Darby, Steven and Gaughan, Luke and Robson, Craig and Mauri, Francesco and Waxman, Jonathan and Sturge, Justin} }