The role of cellular contact and TGF-beta signaling in the activation of the epithelial mesenchymal transition (EMT)

Kelsey Gasior; Nikki J Wagner; Jhon Cores; Rose Caspar; Alyson Wilson; Sudin Bhattacharya; Marlene L Hauck

doi:10.1080/19336918.2018.1526597

The role of cellular contact and TGF-beta signaling in the activation of the epithelial mesenchymal transition (EMT)

Cell Adh Migr. 2019 Dec;13(1):63-75. doi: 10.1080/19336918.2018.1526597. Epub 2018 Oct 8.

Authors

Kelsey Gasior¹, Nikki J Wagner², Jhon Cores³, Rose Caspar², Alyson Wilson⁴, Sudin Bhattacharya^{5

6

7

8

9}, Marlene L Hauck²

Affiliations

¹ a Biomathematics Program , North Carolina State University , Raleigh , NC , USA.
² b College of Veterinary Medicine , North Carolina State University , Raleigh , NC , USA.
³ c Joint Department of Biomedical Engineering , University of North Carolina and North Carolina State University , Chapel Hill , NC , USA.
⁴ d Department of Statistics , North Carolina State University , Raleigh , NC , USA.
⁵ e Department of Biomedical Engineering , Michigan State University , East Lansing , MI , USA.
⁶ f Department of Pharmacology & Toxicology , Michigan State University , East Lansing , MI , USA.
⁷ g Center for Research on Ingredient Safety , Michigan State University , East Lansing , MI , USA.
⁸ h Institute for Quantitative Health Science and Engineering, Michigan State University , East Lansing , MI , USA.
⁹ i Institute for Integrative Toxicology, Michigan State University , East Lansing , MI , USA.

Abstract

The epithelial mesenchymal transition (EMT) is one step in the process through which carcinoma cells metastasize by gaining the cellular mobility associated with mesenchymal cells. This work examines the dual influence of the TGF-β pathway and intercellular contact on the activation of EMT in colon (SW480) and breast (MCF7) carcinoma cells. While the SW480 population revealed an intermediate state between the epithelial and mesenchymal states, the MC7 cells exhibited highly adhesive behavior. However, for both cell lines, an exogenous TGF-β signal and a reduction in cellular confluence can push a subgroup of the population towards the mesenchymal phenotype. Together, these results highlight that, while EMT is induced by the synergy of multiple signals, this activation varies across cell types.

Keywords: EMT; TGF-β; breast carcinoma; cellular adhesion; colon carcinoma; epithelial; mesenchymal.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenocarcinoma / metabolism
Adenocarcinoma / pathology*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology*
Cell Adhesion*
Cell Movement*
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology*
Epithelial-Mesenchymal Transition / drug effects*
Female
Humans
Signal Transduction
Transforming Growth Factor beta / pharmacology*
Tumor Cells, Cultured

Substances

Transforming Growth Factor beta

Grants and funding

We would like to acknowledge the support Dr. Gasior received from the Research Training Group in Mathematical Biology, funded by a National Science Foundation grant RTG/DMS – 1246991, as well as the support Dr. Bhattacharya received from the US EPA STAR Program (EPA Grant Number R835000). Further, we would like to acknowledge the North Carolina State University (NCSU) Cancer Research Enhancement Fund and the NCSU Oncology Fund for partially supporting this research;Environmental Protection Agency [R835000];North Carolina State University Cancer Research Enhancement Fund;