Cytoglobin protects cancer cells from apoptosis by regulation of mitochondrial cardiolipin.

Thorne, Lorna S, Rochford, Garret, Williams, Timothy D, Southam, Andrew D, Rodriguez-Blanco, Giovanny, Dunn, Warwick B ORCID: 0000-0001-6924-0027 and Hodges, Nikolas J
(2021) Cytoglobin protects cancer cells from apoptosis by regulation of mitochondrial cardiolipin. Scientific reports, 11 (1). p. 985.

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Cytoglobin is important in the progression of oral squamous cell carcinoma but the molecular and cellular basis remain to be elucidated. In the current study, we develop a new cell model to study the function of cytoglobin in oral squamous carcinoma and response to cisplatin. Transcriptomic profiling showed cytoglobin mediated changes in expression of genes related to stress response, redox metabolism, mitochondrial function, cell adhesion, and fatty acid metabolism. Cellular and biochemical studies show that cytoglobin expression results in changes to phenotype associated with cancer progression including: increased cellular proliferation, motility and cell cycle progression. Cytoglobin also protects cells from cisplatin-induced apoptosis and oxidative stress with levels of the antioxidant glutathione increased and total and mitochondrial reactive oxygen species levels reduced. The mechanism of cisplatin resistance involved inhibition of caspase 9 activation and cytoglobin protected mitochondria from oxidative stress-induced fission. To understand the mechanism behind these phenotypic changes we employed lipidomic analysis and demonstrate that levels of the redox sensitive and apoptosis regulating cardiolipin are significantly up-regulated in cells expressing cytoglobin. In conclusion, our data shows that cytoglobin expression results in important phenotypic changes that could be exploited by cancer cells in vivo to facilitate disease progression.

Item Type: Article
Uncontrolled Keywords: Cell Line, Mitochondria, Humans, Carcinoma, Squamous Cell, Mouth Neoplasms, Disease Progression, Reactive Oxygen Species, Cardiolipins, Glutathione, Protective Agents, Antioxidants, Cell Adhesion, Cell Cycle, Apoptosis, Cell Proliferation, Up-Regulation, Oxidation-Reduction, Oxidative Stress, Transcriptome, Cytoglobin
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 23 Dec 2021 08:34
Last Modified: 18 Jan 2023 21:18
DOI: 10.1038/s41598-020-79830-w
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