2017
DOI: 10.1101/122051
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EMT and MET: necessary or permissive for metastasis?

Abstract: Epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition (MET) have been often suggested to play crucial roles in metastatic dissemination of carcinomas. Recent studies have revealed that neither of these processes is binary. Instead, carcinoma cells often exhibit a spectrum of epithelial/mesenchymal phenotype(s). While epithelial-mesenchymal plasticity has been observed pre-clinically and clinically, whether any of these phenotypic transitions are indispensable for metas… Show more

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Cited by 78 publications
(92 citation statements)
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References 143 publications
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“…The genetic deletion of Zeb1 associated with PDAC KPC GEMMs also failed to prevent metastasis in 50% of mice (Krebs et al , ). These results support that alternative mechanisms beyond the EMT‐MET program may also support the formation of metastatic lesions (Jolly et al , ). Alternatively, evaluating the role of single transcription factors such as Twist, Snail, and Zeb1 in driving an EMT program and metastasis may insufficiently capture the breadth and complexity of EMT induction in tumors.…”
Section: Discussionsupporting
confidence: 81%
“…The genetic deletion of Zeb1 associated with PDAC KPC GEMMs also failed to prevent metastasis in 50% of mice (Krebs et al , ). These results support that alternative mechanisms beyond the EMT‐MET program may also support the formation of metastatic lesions (Jolly et al , ). Alternatively, evaluating the role of single transcription factors such as Twist, Snail, and Zeb1 in driving an EMT program and metastasis may insufficiently capture the breadth and complexity of EMT induction in tumors.…”
Section: Discussionsupporting
confidence: 81%
“…Lastly, we investigated the correlation of EMT scores with metastatic potential in these TCGA datasets. Breast cancer samples that exhibited metastasis were either categorized as epithelial or hybrid E/M (Figure S6B), reinforcing the concept that a complete EMT need not occur for metastatic dissemination [47]. …”
Section: Resultssupporting
confidence: 58%
“…Characterizing the hybrid E/M phenotype(s) is a crucial step toward addressing recent controversies in the literature. In particular, several recent studies have questioned the indispensable role of at least a complete EMT and MET in metastatic progression [34,47,48]. This model is therefore valuable in investigating systematically the role of hybrid E/M phenotype(s) in the metastatic cascade and can help us appreciate a more nuanced view of cellular plasticity.…”
Section: Discussionmentioning
confidence: 99%
“…The cAMP signalling pathway is one of the many pathways that are implicated in EMT (Bartis, Mise, Mahida, Eickelberg, & Thickett, ; Jansen, Gosens, Wieland, & Schmidt, ; Jolly, Ware, Gilja, Somarelli, & Levine, ; Nieto, ). The EMT process comprises the loss of cell–cell junctions (tight junctions, desmosomes, and adherens junctions) and the loss of cell interactions with the basal membrane.…”
Section: Epithelial‐to‐mesenchymal Transitionmentioning
confidence: 99%
“…The process of EMT is driven by a complex regulatory network beyond the transcriptional level, which integrates epigenetics, alternative splicing, protein stability, and most importantly subcellular localization (Jolly et al, ; Nieto, ). Several lines of evidence indicate that cAMP—a central player in compartmentalized signalling—acts as a potential novel pharmaceutical target in EMT (Kolosionek et al, ; Milara et al, ; Table ).…”
Section: Camp Compartmentalization In Emtmentioning
confidence: 99%