EMT subtype influences epithelial plasticity and mode of cell migration

By Nicole M. Aiello, R. Maddipati, Robert J. Norgard, D. Balli, Jinyang Li, Salina Yuan, Taiji Yamazoe, Taylor A. Black, Amine Sahmoud, E. Furth and 2 more. Developmental Cell, 2018

602 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Genetics, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/1b59e306e155b680e374a0b4991661346d55d671

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In Genetics

1. Yibin Kang
2. Harald Schuhwerk
3. Thomas Brabletz
4. Simone Brabletz
5. Marc P. Stemmler

In Molecular Biology

1. Thomas Brabletz
2. Simone Brabletz
3. Marc P. Stemmler
4. Yibin Kang
5. Wei Dang Lu
6. Harald Schuhwerk
7. Yuhe Huang
8. Xiawei Wei

In Oncology

1. Simone Brabletz
2. Thomas Brabletz
3. Wei Dang Lu
4. Yibin Kang
5. Harald Schuhwerk
6. Marc P. Stemmler
7. Yuhe Huang
8. A. Rustgi

Citations in the corpus

• The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis (2022, methodology): “A recent study using a genealogical labeling approach and sequencing found that CDH1 epithelial protein was internalized in most tumors in the RAB11+ cycle, whereas at the protein level CDH1 mRNA remained unchanged in most cells [195].”
• Dynamic EMT: a multi‐tool for tumor progression (2021, positive): “Neverthe-less, despite the epithelial appearance, either characteristic of a partial EMT is also detectable in these migrating cell clusters (Aiello et al , 2018), or the epithelial clusters follow mesenchymal “leader” cells that pave the way for their more epithelial “follower” cells (Matise et al…”
• Epithelial-mesenchymal plasticity in cancer progression and metastasis (2019, background): “These different EMT programs can lead to different modes of cell invasion during pancreatic cancer progression as shown in a lineage-labeled mouse model (Aiello et al., 2018).”
• EMT, MET, plasticity and tumor metastasis (2020, background): “demonstrated the existence of a pEMT population with co-expression of epithelial and mesenchymal markers that disseminated through collective migration, and a cEMT population that preferentially disseminated as single cells [23].”