Coupling the modules of EMT and stemness: A tunable 'stemness window' model.

Oncotarget
Mohit Kumar JollyHerbert Levine

Abstract

Metastasis of carcinoma involves migration of tumor cells to distant organs and initiate secondary tumors. Migration requires a complete or partial Epithelial-to-Mesenchymal Transition (EMT), and tumor-initiation requires cells possessing stemness. Epithelial cells (E) undergoing a complete EMT to become mesenchymal (M) have been suggested to be more likely to possess stemness. However, recent studies suggest that stemness can also be associated with cells undergoing a partial EMT (hybrid E/M phenotype). Therefore, the correlation between EMT and stemness remains elusive. Here, using a theoretical framework that couples the core EMT and stemness modules (miR-200/ZEB and LIN28/let-7), we demonstrate that the positioning of 'stemness window' on the 'EMT axis' need not be universal; rather it can be fine-tuned. Particularly, we present OVOL as an example of a modulating factor that, due to its coupling with miR-200/ZEB/LIN28/let-7 circuit, fine-tunes the EMT-stemness interplay. Coupling OVOL can inhibit the stemness likelihood of M and elevate that of the hybrid E/M (partial EMT) phenotype, thereby pulling the 'stemness window' away from the M end of 'EMT axis'. Our results unify various apparently contradictory experimental findi...Continue Reading

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Citations

May 3, 2016·Journal of Clinical Medicine·Alexandru Dan GrigoreHerbert Levine
Apr 27, 2017·Physical Biology·Dongya JiaHerbert Levine
Jun 27, 2017·NPJ Breast Cancer·Mohit Kumar JollyHerbert Levine
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Mar 24, 2016·Oncotarget·Mohit Kumar JollyHerbert Levine
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