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Targeting metabolic fluxes reverts metastatic transitions in ovarian cancer

Arora, G and Banerjee, M and Langthasa, J and Bhat, R and Chatterjee, S (2023) Targeting metabolic fluxes reverts metastatic transitions in ovarian cancer. In: iScience, 26 (11).

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Official URL: https://doi.org/10.1016/j.isci.2023.108081


The formation of spheroids during epithelial ovarian cancer progression is correlated with peritoneal metastasis, disease recurrence, and poor prognosis. Although metastasis has been demonstrated to be driven by metabolic changes in transformed cells, mechanistic associations between metabolism and phenotypic transitions remain ill-explored. We performed quantitative proteomics to identify protein signatures associated with three distinct phenotypic morphologies (2D monolayers and two geometrically distinct three-dimensional spheroidal states) of the high-grade serous ovarian cancer line OVCAR-3. We obtained disease-driving phenotype-specific metabolic reaction modules and elucidated gene knockout strategies to reduce metabolic alterations that could drive phenotypic transitions. Exploring the DrugBank database, we identified and evaluated drugs that could impair such transitions and, hence, cancer progression. Finally, we experimentally validated our predictions by confirming the ability of one of our predicted drugs, the neuraminidase inhibitor oseltamivir, to inhibit spheroidogenesis in three ovarian cancer cell lines without any cytotoxic effects on untransformed stromal mesothelia. © 2023 The Authors

Item Type: Journal Article
Publication: iScience
Publisher: Elsevier Inc.
Additional Information: The copyright for this article belongs to the Authors.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 13 Dec 2023 11:09
Last Modified: 13 Dec 2023 11:09
URI: https://eprints.iisc.ac.in/id/eprint/83371

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