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

Rodriguez-Teja, M., Gronau, J. H., Minamidate, A., Darby, Steven, Gaughan, L., Robson, C., Mauri, F., Waxman, J. and Sturge, J. (2015) Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147. Molecular Cancer Research, 13 (3). pp. 538-547. ISSN 1541-7786

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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.

Item Type: Article
Subjects: Sciences
Divisions: Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences
Depositing User: Steven Darby
Date Deposited: 23 Aug 2016 14:46
Last Modified: 06 Feb 2020 10:26
URI: http://sure.sunderland.ac.uk/id/eprint/6566
ORCID for Steven Darby: ORCID iD orcid.org/0000-0002-7226-8634

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