Mercedes Rodriguez-Teja
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
Julian H. Gronau
Ai Minamidate
Steven Darby
Luke Gaughan
Craig Robson
Francesco Mauri
Jonathan Waxman
Dr Justin Sturge J.Sturge@hull.ac.uk
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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.
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
Acceptance Date | Nov 1, 2014 |
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Online Publication Date | Nov 7, 2014 |
Publication Date | 2015-03 |
Deposit Date | Jan 28, 2016 |
Publicly Available Date | Nov 23, 2017 |
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 |
DOI | https://doi.org/10.1158/1541-7786.mcr-14-0344-t |
Keywords | Epithelial-to-mesenchymal transition (EMT) |
Public URL | https://hull-repository.worktribe.com/output/384598 |
Publisher URL | http://mcr.aacrjournals.org/content/13/3/538.long |
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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