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Quantifying the Patterns of Metabolic Plasticity and Heterogeneity along the Epithelial–Hybrid–Mesenchymal Spectrum in Cancer

Muralidharan, S and Sahoo, S and Saha, A and Chandran, S and Majumdar, SS and Mandal, S and Levine, H and Jolly, MK (2022) Quantifying the Patterns of Metabolic Plasticity and Heterogeneity along the Epithelial–Hybrid–Mesenchymal Spectrum in Cancer. In: Biomolecules, 12 (2).

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Official URL: https://doi.org/10.3390/biom12020297


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.

Item Type: Journal Article
Publication: Biomolecules
Publisher: MDPI
Additional Information: The copyright for this article belongs to the Authors.
Keywords: algorithm; AMPK signaling; Article; bladder cancer; cancer survival; colon adenocarcinoma; controlled study; epithelial mesenchymal transition; fatty acid metabolism; gene expression; glycolysis; human; human cell; liver cell carcinoma; major clinical study; metastasis; oxidative phosphorylation; phenotype; RNA sequencing; single cell RNA seq; survival analysis; transcriptomics; tumor metabolism; uvea melanoma; epithelial mesenchymal transition; metabolism; neoplasm, Epithelial-Mesenchymal Transition; Glycolysis; Humans; Metabolic Networks and Pathways; Neoplasms; Oxidative Phosphorylation
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 27 Jun 2022 05:45
Last Modified: 27 Jun 2022 05:45
URI: https://eprints.iisc.ac.in/id/eprint/73895

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