A Transient Metabolic State in Melanoma Persister Cells Mediated by Chemotherapeutic Treatments

Persistence is a transient state that poses an important health concern in cancer therapy. The mechanisms associated with persister phenotypes are highly diverse and complex, and many aspects of persister cell physiology remain to be explored. We applied a melanoma cell line and panel of chemotherap...

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Bibliographic Details
Published in:Frontiers in molecular biosciences 2022-01, Vol.8, p.780192
Main Authors: Karki, Prashant, Angardi, Vahideh, Mier, Juan C, Orman, Mehmet A
Format: Article
Language:English
Subjects:
cancer persisters
chemotherapeutics
drug-tolerance
high-throughput assays
melanoma
metabolomics
Molecular Biosciences
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Summary:Persistence is a transient state that poses an important health concern in cancer therapy. The mechanisms associated with persister phenotypes are highly diverse and complex, and many aspects of persister cell physiology remain to be explored. We applied a melanoma cell line and panel of chemotherapeutic agents to show that melanoma persister cells are not necessarily preexisting dormant cells; in fact, they may be induced by cancer chemotherapeutics. Our metabolomics analysis and phenotype microarray assays further demonstrated a transient upregulation in Krebs cycle metabolism in persister cells. We also verified that targeting electron transport chain activity can significantly reduce melanoma persister levels. The reported metabolic remodeling feature seems to be a conserved characteristic of melanoma persistence, as it has been observed in various melanoma persister subpopulations derived from a diverse range of chemotherapeutics. Elucidating a global metabolic mechanism that contributes to persister survival and reversible switching will ultimately foster the development of novel cancer therapeutic strategies.
ISSN:2296-889X
2296-889X
DOI:10.3389/fmolb.2021.780192