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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Cancer metastasis is the leading cause of cancer-related mortality and the process of the epithelial-to-mesenchymal transition (EMT) is crucial for cancer metastasis. Both partial and complete EMT have been reported to influence the metabolic plasticity of cancer cells in terms of switching among the oxidative phosphorylation, fatty acid oxidation and glycolysis pathways. However, a comprehensive analysis of these major metabolic pathways and their associations with EMT across different cancers is lacking. Here, we analyse more than 180 cancer cell datasets and show the diverse associations of these metabolic pathways with the EMT status of cancer cells. Our bulk data analysis shows that EMT generally positively correlates with glycolysis but negatively with oxidative phosphorylation and fatty acid metabolism. These correlations are also consistent at the level of their molecular master regulators, namely AMPK and HIF1α. Yet, these associations are shown to not be universal. The analysis of single-cell data for EMT induction shows dynamic changes along the different axes of metabolic pathways, consistent with general trends seen in bulk samples. Further, assessing the association of EMT and metabolic activity with patient survival shows that a higher extent of EMT and glycolysis predicts a worse prognosis in many cancers. Together, our results reveal the underlying patterns of metabolic plasticity and heterogeneity as cancer cells traverse through the epithelial–hybrid–mesenchymal spectrum of states.

Details

Title
Quantifying the Patterns of Metabolic Plasticity and Heterogeneity along the Epithelial–Hybrid–Mesenchymal Spectrum in Cancer
Author
Muralidharan, Srinath 1   VIAFID ORCID Logo  ; Sahoo, Sarthak 2   VIAFID ORCID Logo  ; Saha, Aryamaan 1 ; Chandran, Sanjay 1 ; Majumdar, Sauma Suvra 3 ; Mandal, Susmita 2 ; Levine, Herbert 4   VIAFID ORCID Logo  ; Jolly, Mohit Kumar 2   VIAFID ORCID Logo 

 Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036, India; [email protected] (S.M.); [email protected] (A.S.); [email protected] (S.C.) 
 Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India; [email protected] (S.S.); [email protected] (S.M.) 
 Department of Biotechnology, National Institute of Technology, Durgapur 713216, India; [email protected] 
 Centre for Theoretical Biological Physics, Departments of Physics and Bioengineering, Northeastern University, Boston, MA 02115, USA 
First page
297
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
2218273X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2632512570
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.