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.

View publisher note:

Articles of Significant Interest Selected from This Issue by the Editors

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00694-14.

ACKNOWLEDGMENTS

This work was supported by a National Institutes of Health (NIH) R01 grant (5R01-CA127727) to M.A.G.-B. D.S. acknowledges an NIH T32 training grant (5T32-CA009111), an NIH F32 NRSA postdoctoral fellowship (F32-CA165482), and a Department of Defense Prostate Cancer Research Program postdoctoral training award (PC121324). J.A.S. acknowledges an American Cancer Society Postdoctoral Fellowship (PF-11-036-01-DDC).

We thank Andrew Armstrong and Shelton Bradrick for helpful discussions, Nicholas Barrows for assistance with statistics, and Kathryn Ware for her input on EGFR signaling. We acknowledge the Duke University Light Microscopy Core Facility and the Duke University Surgical and Optical Imaging Core Facility, shared resources of the Duke Cancer Institute.

We declare no conflicts of interest.