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

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

Research output: Contribution to journalArticle

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Abstract

Dissemination of epithelial cells is a critical step in metastatic spread. Molecular models of dissemination focus on loss of E-cadherin or repression of cell adhesion through an epithelial to mesenchymal transition (EMT). We sought to define the minimum molecular events necessary to induce dissemination of cells out of primary murine mammary epithelium. Deletion of E-cadherin disrupted epithelial architecture and morphogenesis but only rarely resulted in dissemination. In contrast, expression of the EMT transcription factor Twist1 induced rapid dissemination of cytokeratin-positive epithelial cells. Twist1 induced dramatic transcriptional changes in extracellular compartment and cell-matrix adhesion genes but not in cell-cell adhesion genes. Surprisingly, we observed disseminating cells with membrane-localized E-cadherin and β-catenin, and E-cadherin knockdown strongly inhibited Twist1-induced single cell dissemination. Dissemination can therefore occur with retention of epithelial cell identity. The spread of cancer cells during metastasis could similarly involve activation of an epithelial motility program without requiring a transition from epithelial to mesenchymal character.

Original languageEnglish (US)
Pages (from-to)839-856
Number of pages18
JournalJournal of Cell Biology
Volume204
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

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Cadherins
Epithelial-Mesenchymal Transition
Epithelial Cells
Cell Adhesion
Cell-Matrix Junctions
Catenins
Molecular Models
Keratins
Morphogenesis
Genes
Breast
Transcription Factors
Epithelium
Cell Membrane
Neoplasm Metastasis
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

Shamir, E. R., Pappalardo, E., Jorgens, D., Coutinho, K., Tsai, W. T., Aziz, K., ... Ewald, A. J. (2014). Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. Journal of Cell Biology, 204(5), 839-856. https://doi.org/10.1083/jcb.201306088

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.

In: Journal of Cell Biology, Vol. 204, No. 5, 2014, p. 839-856.

Research output: Contribution to journalArticle

Shamir, ER, Pappalardo, E, Jorgens, D, Coutinho, K, Tsai, WT, Aziz, K, Auer, M, Tran, PT, Bader, JS & Ewald, AJ 2014, 'Twist1-induced dissemination preserves epithelial identity and requires E-cadherin', Journal of Cell Biology, vol. 204, no. 5, pp. 839-856. https://doi.org/10.1083/jcb.201306088
Shamir ER, Pappalardo E, Jorgens D, Coutinho K, Tsai WT, Aziz K et al. Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. Journal of Cell Biology. 2014;204(5):839-856. https://doi.org/10.1083/jcb.201306088
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. / Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. In: Journal of Cell Biology. 2014 ; Vol. 204, No. 5. pp. 839-856.
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