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Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition

Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition


Title: Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition
Author: Halldorsson, Skarphedinn   orcid.org/0000-0003-4337-9252
Rohatgi, Neha   orcid.org/0000-0003-1103-0259
Magnúsdóttir, Manuela
Choudhary, Kumari Sonal   orcid.org/0000-0001-9527-7958
Gudjonsson, Thorarinn   orcid.org/0000-0001-9645-9665
Knutsen, Erik
Barkovskaya, Anna
Hilmarsdottir, Bylgja
Perander, Maria
Mælandsmo, Gunhild M.
... 2 more authors Show all authors
Date: 2017-06
Language: English
Scope: 117-129
University/Institute: Háskóli Íslands
University of Iceland
School: Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Department: Rannsóknarsetur í kerfislíffræði (HÍ)
Center for Systems Biology (UI)
Lífvísindasetur (HÍ)
Biomedical Center (UI)
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2017.03.019
Subject: Cancer Research; Oncology; EMT; Metabolism; Genome scale models; Breast cancer; Krabbameinsrannsóknir; Brjóstakrabbamein; Efnaskipti; Erfðafræði
URI: https://hdl.handle.net/20.500.11815/591

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Citation:

Halldorsson, S., Rohatgi, N., Magnusdottir, M., Choudhary, K. S., Gudjonsson, T., Knutsen, E., . . . Rolfsson, Ó. (2017). Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition. Cancer Letters, 396, 117-129. doi:https://doi.org/10.1016/j.canlet.2017.03.019

Abstract:

Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination.

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