Cellular migration and invasion uncoupled: Increased migration is not an inexorable consequence of epithelial-to-mesenchymal transition

Daneen Schaeffer, Jason A. Somarelli, Gabi Hanna, Gregory M. Palmer, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Metastatic dissemination requires carcinoma cells to detach from the primary tumor and invade through the basement membrane. To acquire these characteristics, epithelial tumor cells undergo epithelial-to-mesenchymal transitions (EMT), whereby cells lose polarity and E-cadherin-mediated cell-cell adhesion. Post-EMT cells have also been shown, or assumed, to be more migratory; however, there have been contradictory reports on an immortalized human mammary epithelial cell line (HMLE) that underwent EMT. In the context of carcinoma-associated EMT, it is not yet clear whether the change in migration and invasion must be positively correlated during EMT or whether enhanced migration is a necessary consequence of having undergone EMT. Here, we report that pre-EMT rat prostate cancer (PC) and HMLE cells are more migratory than their post-EMT counterparts. To determine a mechanism for increased epithelial cell migration, gene expression analysis was performed and revealed an increase in epidermal growth factor receptor (EGFR) expression in pre-EMT cells. Indeed, inhibition of EGFR in PC epithelial cells slowed migration. Importantly, while post-EMT PC and HMLE cell lines are less migratory, both remain invasive in vitro and, for PC cells, in vivo. Our study demonstrates that enhanced migration is not a phenotypic requirement of EMT, and migration and invasion can be uncoupled during carcinoma-associated EMT.

Original languageEnglish (US)
Pages (from-to)3486-3499
Number of pages14
JournalMolecular and Cellular Biology
Volume34
Issue number18
DOIs
StatePublished - 2014
Externally publishedYes

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Epithelial-Mesenchymal Transition
Epithelial Cells
Prostatic Neoplasms
Cell Line
Carcinoma
Epidermal Growth Factor Receptor
Cell Movement
Breast Neoplasms
Cell Polarity
Cadherins
Basement Membrane
Cell Adhesion
Neoplasms
Breast

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Cellular migration and invasion uncoupled : Increased migration is not an inexorable consequence of epithelial-to-mesenchymal transition. / Schaeffer, Daneen; Somarelli, Jason A.; Hanna, Gabi; Palmer, Gregory M.; Garcia-Blanco, Mariano.

In: Molecular and Cellular Biology, Vol. 34, No. 18, 2014, p. 3486-3499.

Research output: Contribution to journalArticle

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