Chapter 1
A Spectrum of Cell States During the Epithelial-toMesenchymal Transition
Erica J. Hutchins and Marianne E. Bronner
Abstract
The epithelial-to-mesenchymal transition (EMT) encompasses a complex cascade of events through which
a cell transits to reduce its epithelial characteristics and become migratory. Classically, this transition has
been considered complete upon loss of molecular markers characteristic of an “epithelial” state and
acquisition of those associated with “mesenchymal” cells. Recently, however, evidence from both developmental and cancer EMT contexts suggest that cells undergoing EMT are often heterogeneous, concomitantly expressing both epithelial and mesenchymal markers to varying degrees; rather, cells frequently
display a “partial” EMT phenotype and do not necessarily require full “mesenchymalization” to become
migratory. Here, we offer a brief perspective on recent important advances in our fundamental understanding of the spectrum of cellular states that occur during partial EMT in the context of development and
cancer metastasis.
Key words Epithelial-to-mesenchymal transition, Partial EMT, Cancer, Post-transcriptional regulation, Heterogeneity
1 Perspective
The complex process of the epithelial-to-mesenchymal transition
(EMT) has reiterative roles throughout embryonic morphogenesis
to generate the myriad of tissues and organ systems needed to form
the adult organism. Developmental EMT is analogous in many
ways to the EMT that occurs during cancer metastasis and invasion,
requiring the same signaling pathways as well as often the same
effector genes [1–3]. The process of EMT (both developmentally
and during metastasis) requires cells to coordinately orchestrate a
complex series of intra- and extra-cellular events to achieve separation from the epithelium and become migratory [3, 4]. In traditional descriptions of EMT, the transition was thought to have a
specific, intrinsic end-point—the point at which a cell has
completely lost all “epithelial” markers (e.g., E-cadherin) and
gained a cadre of “mesenchymal” markers (e.g., N-cadherin,
Kyra Campbell and Eric Theveneau (eds.), The Epithelial-to Mesenchymal Transition: Methods and Protocols,
Methods in Molecular Biology, vol. 2179, https://doi.org/10.1007/978-1-0716-0779-4_1,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
3
A Spectrum of Cell States During the Epithelial-toMesenchymal Transition
Erica J. Hutchins and Marianne E. Bronner
Abstract
The epithelial-to-mesenchymal transition (EMT) encompasses a complex cascade of events through which
a cell transits to reduce its epithelial characteristics and become migratory. Classically, this transition has
been considered complete upon loss of molecular markers characteristic of an “epithelial” state and
acquisition of those associated with “mesenchymal” cells. Recently, however, evidence from both developmental and cancer EMT contexts suggest that cells undergoing EMT are often heterogeneous, concomitantly expressing both epithelial and mesenchymal markers to varying degrees; rather, cells frequently
display a “partial” EMT phenotype and do not necessarily require full “mesenchymalization” to become
migratory. Here, we offer a brief perspective on recent important advances in our fundamental understanding of the spectrum of cellular states that occur during partial EMT in the context of development and
cancer metastasis.
Key words Epithelial-to-mesenchymal transition, Partial EMT, Cancer, Post-transcriptional regulation, Heterogeneity
1 Perspective
The complex process of the epithelial-to-mesenchymal transition
(EMT) has reiterative roles throughout embryonic morphogenesis
to generate the myriad of tissues and organ systems needed to form
the adult organism. Developmental EMT is analogous in many
ways to the EMT that occurs during cancer metastasis and invasion,
requiring the same signaling pathways as well as often the same
effector genes [1–3]. The process of EMT (both developmentally
and during metastasis) requires cells to coordinately orchestrate a
complex series of intra- and extra-cellular events to achieve separation from the epithelium and become migratory [3, 4]. In traditional descriptions of EMT, the transition was thought to have a
specific, intrinsic end-point—the point at which a cell has
completely lost all “epithelial” markers (e.g., E-cadherin) and
gained a cadre of “mesenchymal” markers (e.g., N-cadherin,
Kyra Campbell and Eric Theveneau (eds.), The Epithelial-to Mesenchymal Transition: Methods and Protocols,
Methods in Molecular Biology, vol. 2179, https://doi.org/10.1007/978-1-0716-0779-4_1,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
3