Twist1-induced dissemination preserves epithelial identity and requires E-cadherin

Shamir, Eliah R.; Pappalardo, Elisa; Jorgens, Danielle; Coutinho, Kester; Tsai, Wen Ting; Aziz, Khaled; Auer, Manfred; Tran, Phuoc T.; Bader, Joel S.; Ewald, Andrew J.

doi:10.1083/jcb.201306088

Cited by 180 publications

(198 citation statements)

References 60 publications

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“…For example, activation of epithelial-mesenchymal transition within the mammary gland by overexpression of Twist1 triggers rapid cell dissemination and a breakdown in cell positioning within the gland. Surprisingly, expression profiling revealed that these architectural changes coincided with an up-regulation of basal adhesion machinery rather than alterations in cell-cell cohesion (18). Second, our model predicts that processes that lead to ductal swelling and lumen filling owing to aberrant luminal cell growth would decrease the tissue surface to volume ratio (e.g., changing the parameter ∅ðrÞ; SI Appendix), thereby decreasing the influence of the tissue boundary on cell positioning.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, normal levels of tissue heterogeneity do not affect cell positioning in the gland. Even when heterogeneity in cell-cell cohesion is artificially elevated by mosaic deletion of E-cadherin, LEP and MEP retain their relative positions efficiently (18). How self-organization remains robust among these and other heterogeneous populations of cells is poorly understood.…”

Section: Significancementioning

confidence: 99%

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A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Cerchiari

Garbe

Jee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

102

120

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Developing tissues contain motile populations of cells that can selforganize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its selforganization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue-ECM boundary, rather than by differential homo-and heterotypic energies of cell-cell interaction. Surprisingly, interactions with the tissue-ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell-cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell-cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell-ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer.heterogeneity | cell sorting | differential adhesion | mammary | prostate S elf-organization is a process that contributes to pattern formation and repair at all scales of biological complexity. At the tissue scale, defining robust strategies of self-organization is critical for engineering functional tissues, as well as for understanding development and the breakdown of tissue structure during diseases such as cancer (1). During development, two or more populations of motile cells can self-organize into spatially ordered tissues by a process referred to as cell sorting (2-4). The outcome of cell sorting can be rationalized using physical models that invoke cell-type-specific differences in interfacial energies. Interfacial energies arise through the action of a contractile cell cortex coupled to adhesion molecules (e.g., cadherins) that link the cortices of neighboring cells and signal to modulate cortical tension at specific cellular interfaces (5). In general, the organization of a tissue after cell sorting corresponds to a configuration that maximizes the formation of the most energetically favorable (hereafter referred to as most cell-cell cohesive) † cellular interfaces (6). For example, with an intermediate level of heterotypic cell-cell cohesion the most self-cohesive cell type is typically found in the tissue core, with the le...

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Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Cerchiari

Garbe

Jee³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

102

120

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“…E-cadherin has long been considered as a protein that assures the static behaviour of epithelial cells and repression of which is necessary for epithelial cells to become mesenchymal and migratory; however, the situation has turned out to be more complicated. Not only can cells adopt many mesenchymal features, including migration, while actively transcribing E-cadherin (Campbell and Casanova, 2015;Campbell et al, 2011;Dumortier et al, 2012;Montero et al, 2005;Shamir et al, 2014;Theveneau and Mayor, 2012), there is an increasing number of cases in which the downregulation of E-cadherin in migrating cells leads to a complete block in their migration (Cai et al, 2014;Kardash et al, 2010;Montero et al, 2005;Niewiadomska et al, 1999;Shamir et al, 2014), suggesting that E-cadherin is not simply required for static adhesion but, conversely, that it is also a highly dynamic component actively required for cell migration. In fact, a recent study showed that this is indeed the case in Drosophila border cells, where a novel role for E-cadherin as an integrator of mechanical signals during the directional migration of cell clusters was revealed (Cai et al, 2014).…”

Section: The Complex Relationship Between E-cadherin and Migratory Camentioning

confidence: 99%

A common framework for EMT and collective cell migration

2016

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During development, cells often switch between static and migratory behaviours. Such transitions are fundamental events in development and are linked to harmful consequences in pathology. It has long been considered that epithelial cells either migrate collectively as epithelial cells, or undergo an epithelial-to-mesenchymal transition and migrate as individual mesenchymal cells. Here, we assess what is currently known about in vivo cell migratory phenomena and hypothesise that such migratory behaviours do not fit into alternative and mutually exclusive categories. Rather, we propose that these categories can be viewed as the most extreme cases of a general continuum of morphological variety, with cells harbouring different degrees or combinations of epithelial and mesenchymal features and displaying an array of migratory behaviours.

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“…The results from both studies suggest that EMT enhances chemoresistance but does not affect cellular motility or metastatic potential. Moreover, overexpression of Twist1 contributes to dissemination of breast cancer cells in a manner that requires the expression of E-cadherin and does not disrupt epithelial layer integrity or requires induction of the EMT (Shamir et al, 2014).…”

Section: The Airway Epithelium and Its Pivotal Role In Asthmamentioning

confidence: 99%

Collective migration and cell jamming in asthma, cancer and development

Park

Atia

Mitchel

et al. 2016

Journal of Cell Science

138

169

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Collective cellular migration within the epithelial layer impacts upon development, wound healing and cancer invasion, but remains poorly understood. Prevailing conceptual frameworks tend to focus on the isolated role of each particular underlying factor -taken one at a time or at most a few at a time -and thus might not be tailored to describe a cellular collective that embodies a wide palette of physical and molecular interactions that are both strong and complex. To bridge this gap, we shift the spotlight to the emerging concept of cell jamming, which points to only a small set of parameters that govern when a cellular collective might jam and rigidify like a solid, or instead unjam and flow like a fluid. As gateways to cellular migration, the unjamming transition (UJT) and the epithelial-to-mesenchymal transition (EMT) share certain superficial similarities, but their congruence -or lack thereof -remains unclear. In this Commentary, we discuss aspects of cell jamming, its established role in human epithelial cell layers derived from the airways of nonasthmatic and asthmatic donors, and its speculative but emerging roles in development and cancer cell invasion.

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Twist1-induced dissemination preserves epithelial identity and requires E-cadherin

Abstract: Expression of the transcription factor Twist1 induces dissemination of normal mammary epithelial cells without changing the RNA levels of epithelial-specific genes such as E-cadherin.

Cited by 180 publications

References 60 publications

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

A common framework for EMT and collective cell migration

Collective migration and cell jamming in asthma, cancer and development

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