Epithelial–mesenchymal plasticity: emerging parallels between tissue morphogenesis and cancer metastasis

Plygawko, Andrew T.; Kan, Shohei; Campbell, Kyra

doi:10.1098/rstb.2020.0087

Cited by 44 publications

(30 citation statements)

References 113 publications

(177 reference statements)

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“…Note that H 2 cells cannot disseminate alone without the help of higher motile H 1 cells, since for Γ = 3 the minimum motile forces required to disseminate cells μ min > 20). This finding is somewhat analogous to experimental cases where non-cancerous cells like fibroblasts can help to release the cells with lower motility (more epithelial like) [40, 46]. Although the H 1 cells help H 2 cells to disseminate, they cannot maintain contact with the H 2 cells due to their high difference in motile forces.…”

Section: Resultssupporting

confidence: 69%

Cluster Size Distribution of Cells Disseminating from a Primary Tumor

Mukherjee

Levine

2021

Preprint

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The first stage of the metastatic cascade often involves motile cells emerging from a primary tumor either as single cells or as clusters. These cells enter the circulation, transit to other parts of the body and finally are responsible for growth of secondary tumors in distant organs. The mode of dissemination is believed to depend on the EMT nature (epithelial, hybrid or mesenchymal) of the cells. Here, we calculate the cluster size distribution of these migrating cells, using a mechanistic computational model, in presence of different degree of EMT-ness of the cells; EMT is treated as given rise to changes in their active motile forces ($\mu$) and cell-medium surface tension ($\Gamma$). We find that, for ($\mu>\mu_{min},\ \Gamma>1$), when the cells are hybrid in nature, the mean cluster size, $\overline{N} \sim \Gamma^{1.98}/\mu^{2.75}$, where $\mu_{min}$ increases with increase in $\Gamma$. For $\Gamma \leq 0$, $\overline{N}=1$, the cells behave as completely mesenchymal. In presence of spectrum of hybrid states with different degree of EMT-ness (motility) in primary tumor, the cells which are relatively more mesenchymal (higher $\mu$) in nature, form larger clusters, whereas the smaller clusters are relatively more epithelial (lower $\mu$). Moreover, the heterogeneity in $\mu$ is comparatively higher for smaller clusters with respect to that for larger clusters. We also observe that more extended cell shapes promote the formation of smaller clusters. Overall, this study establishes a framework which connects the nature and size of migrating clusters disseminating from a primary tumor with the phenotypic composition of the tumor, and can lead to the better understanding of metastasis.

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Section: Resultssupporting

confidence: 69%

Cluster Size Distribution of Cells Disseminating from a Primary Tumor

Mukherjee

Levine

2021

Preprint

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“…In addition, this process is reversible, as is also reported for bilaterians: incubation in natural sea water induces cell-reaggregation and re-epithelialization with a complete restoration of cell polarity, cell-cell and cell-matrix contacts. Such a plasticity of epithelial tissues is essential since epithelial cell movements are required during major morphogenetic processes such as, for example, wound healing and regeneration, tissue renewal, or gastrulation (Donati and Watt, 2015;Kim et al, 2017;Nieto, 2013;Plygawko et al, 2020). In bilaterians, calcium signaling is commonly and naturally involved in the regulation of epithelial tissue properties (motility, differentiation, cilia beating) during developmental processes (Brodskiy and Zartman, 2018).…”

Section: Calcium As Key Regulator For Epithelium Morphogenesismentioning

confidence: 99%

Evolution of mechanisms controlling epithelial morphogenesis across animals: new insights from dissociation - reaggregation experiments in the sponge Oscarella lobularis

Vernale

Prünster

Marchianò

et al. 2021

Preprint

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Background: The ancestral presence of epithelia in Metazoa is no longer debated. Even though Porifera seem to be the best candidates to be the sister group to all other Metazoa, hardly anything is known about the proteins involved in the composition of cell-cell junctions or about the mechanisms that regulate epithelial morphogenetic processes in this phylum. Results: To get insights into the early evolution of epithelial morphogenesis, we focused on morphogenic characteristics of the homoscleromorph sponge Oscarella lobularis. Homoscleromorpha are a sponge class with a typical basement membrane and adherens-like junctions unknown in other sponge classes. We took advantage of the dynamic context provided by cell dissociation-reaggregation experiments to explore morphogenetic processes in epithelial cells in an early lineage by combining fluorescent and electronic microscopy observations and RNA sequencing approaches at key time-points of the dissociation and reaggregation processes. Conclusions: Our results show that part of the molecular toolkit involved in the loss and restoration of epithelial features such as cell-cell and cell-matrix adhesion is conserved between Homoscleromorpha and Bilateria, suggesting their common role in the last common ancestor of animals. In addition, Sponge-specific genes are differently expressed during the dissociation and reaggregation processes, calling for future functional characterization of these genes.

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“…Mechanistic links between symmetry breaking and morphogenesis are explored in a number of contexts, including how actin flows drive polarity formation in the Caenorhabditis elegans zygote [20], asymmetric patterning in lineage segregation during early mouse development [21], and how mechanical asymmetries promote tissue folding [22]. Finally, we review how changes in cell states from epithelial to mesenchymal (and vice versa) are controlled and coordinated to facilitate tissue morphogenesis [23].…”

Section: Structure and Overview Of Contributionsmentioning

confidence: 99%