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Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer

1
Department of Chemistry and Biochemistry, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46617, USA
2
Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN 47405, USA
3
Department of Applied and Computational Mathematics and Statistics, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46617, USA
4
Department of Mathematics, University of California Riverside, Riverside, CA 92521, USA
*
Author to whom correspondence should be addressed.
Cancers 2017, 9(8), 104; https://doi.org/10.3390/cancers9080104
Received: 9 June 2017 / Revised: 2 August 2017 / Accepted: 6 August 2017 / Published: 9 August 2017
(This article belongs to the Special Issue The Epithelial-to-Mesenchymal Transition (EMT) in Cancer)
Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases. This exceptional microenvironment is highly permissive for phenotypic plasticity, enabling mesenchymal-to-epithelial (MET) and epithelial-to-mesenchymal (EMT) transitions. In this review, we summarize current knowledge on EOC heterogeneity in an EMT context, outline major regulators of EMT in ovarian cancer, address controversies in EMT and EOC chemoresistance, and highlight computational modeling approaches toward understanding EMT/MET in EOC. View Full-Text
Keywords: ovarian cancer; intraperitoneal metastasis; cadherins; heterogeneity; epithelial-to-mesenchymal transition (EMT); mesenchymal-to-epithelial transition (MET); intraperitoneal tumor microenvironment; computational modeling of EMT ovarian cancer; intraperitoneal metastasis; cadherins; heterogeneity; epithelial-to-mesenchymal transition (EMT); mesenchymal-to-epithelial transition (MET); intraperitoneal tumor microenvironment; computational modeling of EMT
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Klymenko, Y.; Kim, O.; Stack, M.S. Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer. Cancers 2017, 9, 104.

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