EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2018 Jun 20

PMID 29920274

Citations 350

Authors

Nicole M Aiello

Ravikanth Maddipati

Robert J Norgard

David Balli

Jinyang Li

Salina Yuan

Taiji Yamazoe

Taylor Black

Amine Sahmoud

Emma E Furth

Dafna Bar-Sagi

Ben Z Stanger

Affiliations

Soon will be listed here.

Abstract

Epithelial-mesenchymal transition (EMT) is strongly implicated in tumor cell invasion and metastasis. EMT is thought to be regulated primarily at the transcriptional level through the repressive activity of EMT transcription factors. However, these classical mechanisms have been parsed out almost exclusively in vitro, leaving questions about the programs driving EMT in physiological contexts. Here, using a lineage-labeled mouse model of pancreatic ductal adenocarcinoma to study EMT in vivo, we found that most tumors lose their epithelial phenotype through an alternative program involving protein internalization rather than transcriptional repression, resulting in a "partial EMT" phenotype. Carcinoma cells utilizing this program migrate as clusters, contrasting with the single-cell migration pattern associated with traditionally defined EMT mechanisms. Moreover, many breast and colorectal cancer cell lines utilize this alternative program to undergo EMT. Collectively, these results suggest that carcinoma cells have different ways of losing their epithelial program, resulting in distinct modes of invasion and dissemination.

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