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Survival outcome and EMT suppression mediated by a lectin domain interaction of Endo180 and CD147

Rodriguez-Teja, Mercedes; Gronau, Julian H.; Minamidate, Ai; Darby, Steven; Gaughan, Luke; Robson, Craig; Mauri, Francesco; Waxman, Jonathan; Sturge, Justin

Authors

Mercedes Rodriguez-Teja

Julian H. Gronau

Ai Minamidate

Steven Darby

Luke Gaughan

Craig Robson

Francesco Mauri

Jonathan Waxman

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.

Publication Date 2015-03
Journal Molecular cancer research
Print ISSN 1541-7786
Electronic ISSN 1557-3125
Publisher American Association for Cancer Research
Peer Reviewed Peer Reviewed
Volume 13
Issue 3
Pages 538-547
Institution Citation Rodriguez-Teja, M., Gronau, J. H., Minamidate, A., Darby, S., Gaughan, L., Robson, C., …Sturge, J. (2015). Survival outcome and EMT suppression mediated by a lectin domain interaction of Endo180 and CD147. Molecular cancer research, 13(3), 538-547. https://doi.org/10.1158/1541-7786.mcr-14-0344-t
DOI https://doi.org/10.1158/1541-7786.mcr-14-0344-t
Keywords Epithelial-to-mesenchymal transition (EMT)
Publisher URL http://mcr.aacrjournals.org/content/13/3/538.long
Copyright Statement ©2016 University of Hull
Additional Information This is the authors accepted manuscript of an article published in Molecular cancer research, 2015, v.13 issue 3.

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