2014
DOI: 10.1098/rsif.2014.0962
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Towards elucidating the connection between epithelial–mesenchymal transitions and stemness

Abstract: Epithelial cells undergoing epithelial-to-mesenchymal transitions have often been shown to behave as cancer stem cells, but the precise molecular connection remains elusive. At the genetic level, stemness is governed by LIN28/let-7 double inhibition switch, whereas EMT/MET is controlled by miR-200/ZEB double inhibition circuit and LIN28 is inhibited by miR-200, coupling the two modules. Here, using a specially devised theoretical framework to investigate the dynamics of the LIN28/let-7 system, we show that it … Show more

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Cited by 178 publications
(188 citation statements)
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“…The emergence of a hybrid tip/stalk phenotype also lends support to the emerging notion "a black and white distinction between tip and stalk cells is an oversimplification" (1) and strengthens the increasingly accepted notion that a hybrid state that coexpresses markers of two lineages is a signature of enhanced plasticity (multipotency) of a system (41)(42)(43). We find that the tendency to adopt this hybrid phenotype is reduced at high levels of Fringe, a glycosyltransferase that promotes Notch-Delta signaling at the expense of Notch-Jagged signaling by modifying Notch to increase its affinity for Delta and decrease it for Jagged.…”
Section: Discussionmentioning
confidence: 76%
“…The emergence of a hybrid tip/stalk phenotype also lends support to the emerging notion "a black and white distinction between tip and stalk cells is an oversimplification" (1) and strengthens the increasingly accepted notion that a hybrid state that coexpresses markers of two lineages is a signature of enhanced plasticity (multipotency) of a system (41)(42)(43). We find that the tendency to adopt this hybrid phenotype is reduced at high levels of Fringe, a glycosyltransferase that promotes Notch-Delta signaling at the expense of Notch-Jagged signaling by modifying Notch to increase its affinity for Delta and decrease it for Jagged.…”
Section: Discussionmentioning
confidence: 76%
“…Specifically, we expect that Notch-Jagged signaling between these cells helps them to maintain that otherwise metastable hybrid epithelial/mesenchymal (E/M) phenotype. As has been recently observed in clusters of circulating tumor cells (CTCs), these hybrid E/M cells mediate tumor aggression and invasion (58), and can have more metastatic potential than the CTCs moving individually (59,60). Future theoretical studies should investigate the coupling of EMT and Notch-Delta-Jagged signaling to explore this hypothesis.…”
Section: Discussionmentioning
confidence: 99%
“…By integrating some cancer or stem cell-related core circuits (8,(24)(25)(26)(27)(28)(29), we constructed a simplified gene network of cancer and development ( Fig. 1), which includes 6 gene nodes (Supplementary Table S1) and 16 edges (7 activation regulations and 9 repression regulations).…”
Section: Model Of Gene Regulatory Network For Cancer and Developmentmentioning
confidence: 99%