Hybrid epithelial/mesenchymal phenotype(s): The 'fittest' for metastasis?

Biochimica Et Biophysica Acta. Reviews on Cancer
Mohit Kumar JollyHerbert Levine

Abstract

Metastasis is the leading cause of mortality among cancer patients. Dissemination enabled by an epithelial-to-mesenchymal transition (EMT) of carcinoma cells has long been considered to be the predominant mechanism for carcinoma metastasis, based on overexpression studies of many EMT-inducing transcription factors. Individual CTCs - and a binary framework of EMT - have been long considered to be sufficient and necessary condition for metastasis. However, recent studies have shown that collective migration and invasion through tumor buds and clusters of Circulating Tumor Cells (CTCs) as possibly being the prevalent mode of metastasis, although individual CTCs may still contribute to metastasis. These strands and clusters have been proposed to often exhibit a hybrid epithelial/mesenchymal (E/M) phenotype where cells retain epithelial traits of cell-cell adhesion and simultaneously gain mesenchymal characteristics of migration and invasion. To highlight the crucial questions regarding metastasis, we define EMT in a non-binary and context-specific manner, suggest that it can be viewed as a trans-differentiation process, and illustrate the implications of hybrid E/M phenotype(s) and cluster-based dissemination in metastasis.

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Citations

Dec 18, 2018·Physical Biology·Dongya JiaHerbert Levine
Dec 12, 2018·Physical Biology·Kuheli BiswasAnandamohan Ghosh
May 20, 2019·Radiology and Oncology·Taja LozarTanja Jesenko
Aug 30, 2019·Cells·Elisabetta Rossi, Francesco Fabbri
Dec 13, 2019·Cellular Oncology (Dordrecht)·Meysam YousefiSeyed H Ghaffari
Oct 1, 2020·Journal of the Royal Society, Interface·Atchuta Srinivas DudduMohit Kumar Jolly
Sep 29, 2019·Journal of Clinical Medicine·Mohit Kumar Jolly, Toni Celià-Terrassa
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May 20, 2020·NPJ Systems Biology and Applications·Kishore HariMohit Kumar Jolly
Dec 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Federico BocciMohit Kumar Jolly
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