Data from Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147

Abstract

<div>Abstract<p>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.</p><p><b>Implications:</b> This study identifies the interaction between CTLD4 in Endo180 and CD147 as an EMT suppressor and indicates that stabilization of this molecular complex improves prostate cancer survival rates.</p><p><b>Visual Overview:</b> <a href="http://mcr.aacrjournals.org/content/13/3/538/F1.large.jpg" target="_blank">http://mcr.aacrjournals.org/content/13/3/538/F1.large.jpg</a></p><p><i>Mol Cancer Res; 13(3); 538–47. ©2014 AACR</i>.</p></div>