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• W2949145420 abstract "The Epithelial-Mesenchymal Transition (EMT) endows epithelial-looking cells with enhanced migratory ability during embryonic development and tissue repair. EMT can also be co-opted by cancer cells to acquire metastatic potential and drug-resistance. Recent research has argued that epithelial (E) cells can undergo either a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype that typically displays collective migration, or a complete EMT to adopt a mesenchymal (M) phenotype that shows individual migration. The core EMT regulatory network - miR-34/SNAIL/miR-200/ZEB1 - has been identified by various studies, but how this network regulates the transitions among the E, E/M, and M phenotypes remains controversial. Two major mathematical models - ternary chimera switch (TCS) and cascading bistable switches (CBS) - that both focus on the miR-34/SNAIL/miR-200/ZEB1 network, have been proposed to elucidate the EMT dynamics, but a detailed analysis of how well either or both of these two models can capture recent experimental observations about EMT dynamics remains to be done.Here, via an integrated experimental and theoretical approach, we first show that both these two models can be used to understand the two-step transition of EMT - E→E/M→M, the different responses of SNAIL and ZEB1 to exogenous TGF-β and the irreversibility of complete EMT. Next, we present new experimental results that tend to discriminate between these two models. We show that ZEB1 is present at intermediate levels in the hybrid E/M H1975 cells, and that in HMLE cells, overexpression of SNAIL is not sufficient to initiate EMT in the absence of ZEB1 and FOXC2.These experimental results argue in favor of the TCS model proposing that miR-200/ZEB1 behaves as a three-way decision-making switch enabling transitions among the E, hybrid E/M and M phenotypes." @default.
• W2949145420 created "2019-06-27" @default.
• W2949145420 creator A5012321109 @default.
• W2949145420 creator A5015852015 @default.
• W2949145420 creator A5030987631 @default.
• W2949145420 creator A5033841777 @default.
• W2949145420 creator A5036939761 @default.
• W2949145420 creator A5040156444 @default.
• W2949145420 creator A5044963873 @default.
• W2949145420 creator A5050198314 @default.
• W2949145420 creator A5060687079 @default.
• W2949145420 creator A5074771115 @default.
• W2949145420 creator A5078596004 @default.
• W2949145420 creator A5079027078 @default.
• W2949145420 creator A5083772852 @default.
• W2949145420 date "2017-11-01" @default.
• W2949145420 modified "2023-10-16" @default.
• W2949145420 title "Distinguishing mechanisms underlying EMT tristability" @default.
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