TY - JOUR
T1 - The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems
AU - Leggett, Susan E.
AU - Hruska, Alex M.
AU - Guo, Ming
AU - Wong, Ian Y.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression. [MediaObject not available: see fulltext.].
AB - The epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression. [MediaObject not available: see fulltext.].
KW - Actin
KW - Collective migration
KW - Cytoskeleton
KW - Extracellular matrix
KW - Vimentin
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UR - http://www.scopus.com/inward/citedby.url?scp=85102246955&partnerID=8YFLogxK
U2 - 10.1186/s12964-021-00713-2
DO - 10.1186/s12964-021-00713-2
M3 - Review article
C2 - 33691719
AN - SCOPUS:85102246955
SN - 1478-811X
VL - 19
JO - Cell Communication and Signaling
JF - Cell Communication and Signaling
IS - 1
M1 - 32
ER -