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Review
. 2019 May 6;216(5):1016-1026.
doi: 10.1084/jem.20181827. Epub 2019 Apr 11.

Context-dependent EMT programs in cancer metastasis

Nicole M Aiello  1 , Yibin Kang  2
Affiliations
Review

Context-dependent EMT programs in cancer metastasis

Nicole M Aiello et al. J Exp Med. .

Abstract

Epithelial-mesenchymal transition (EMT) is a developmental process whereby stationary, adherent cells acquire the ability to migrate. EMT is critical for dramatic cellular movements during embryogenesis; however, tumor cells can reactivate EMT programs, which increases their aggressiveness. In addition to motility, EMT is associated with enhanced stem cell properties and drug resistance; thus it can drive metastasis, tumor recurrence, and therapy resistance in the context of cancer. However, the precise requirements for EMT in metastasis have not been fully delineated, with different tumor types relying on discrete EMT effectors. Most tumor cells do not undergo a full EMT, but rather adopt some qualities of mesenchymal cells and maintain some epithelial characteristics. Emerging evidence suggests that partial EMT can drive distinct migratory properties and enhance the epithelial-mesenchymal plasticity of cancer cells as well as cell fate plasticity. This review discusses the diverse regulatory mechanisms and functional consequences of EMT, with an emphasis on the importance of partial EMT.

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Figures

Figure 1.
Figure 1.
Layers of EMT regulation. EMT is regulated at the epigenetic, transcriptional, posttranscriptional, translational, and posttranslational levels. EMT-TFs recruit DNA methylation and histone modification machinery to stably repress epithelial genes and prevent their transcription. They are opposed by epithelial-associated TFs, which in turn repress EMT-TFs. Both epithelial and mesenchymal transcripts are alternatively spliced and regulated by miRNAs and lncRNAs. Translation initiation, mRNA stability, and polyadenylation affect the translation rate of epithelial and mesenchymal transcripts. Posttranslational modifications such as ubiquitylation, acetylation, and phosphorylation determine the balance between stability and degradation of epithelial and mesenchymal proteins.
Figure 2.
Figure 2.
Partial EMT: Heterogeneity and functional consequences. EMT is a spectrum of epithelial and mesenchymal phenotypes. Partial EMT, which typically involves a combination of epithelial and mesenchymal gene expression, facilitates cluster migration/dissemination, plasticity between epithelial and mesenchymal states, and even plasticity in cell fate (i.e., transdifferentiation to adipocytes).
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