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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Schaeffer, D; Somarelli, JA; Hanna, G; Palmer, GM; Garcia-Blanco, MA

Published Date

  • September 15, 2014

Published In

Volume / Issue

  • 34 / 18

Start / End Page

  • 3486 - 3499

PubMed ID

  • 25002532

Pubmed Central ID

  • PMC4135620

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

Digital Object Identifier (DOI)

  • 10.1128/MCB.00694-14

Language

  • eng

Conference Location

  • United States