title: Cellular migration and invasion uncoupled: increased migration is not an inexorable consequence of epithelial-to-mesenchymal transition.
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.
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, North Carolina, USA Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Daneen
authors.initials: D
authors.lastname: Schaeffer
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, North Carolina, USA Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Somarelli
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Gabi
authors.initials: G
authors.lastname: Hanna
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Palmer
authors.affiliation: Center for RNA Biology, Duke University Medical Center, Durham, North Carolina, USA Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA Program in Molecular Genetics and Genomics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA m.garciablanco@duke.edu.
authors.forename: Mariano A
authors.initials: MA
authors.lastname: Garcia-Blanco
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats
chemical_list: D066246:ErbB Receptors