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

Abstract

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.

Review: The Key Factors to Melanomagenesis

“…Persister melanoma cells are considered dormant cells in a mass of cancer cells that can tolerate a high level of drugs [ 58 ]. A study by Karki et al attests that persister cells could be induced by chemotherapy [ 58 ].…”

“…Persister melanoma cells are considered dormant cells in a mass of cancer cells that can tolerate a high level of drugs [ 58 ]. A study by Karki et al attests that persister cells could be induced by chemotherapy [ 58 ]. These cells experience metabolic alteration to improve the survival of tumoral cells, sustain cell proliferation, avoid the action of drugs, and fulfill energy requirements [ 58 ].…”

“…A study by Karki et al attests that persister cells could be induced by chemotherapy [ 58 ]. These cells experience metabolic alteration to improve the survival of tumoral cells, sustain cell proliferation, avoid the action of drugs, and fulfill energy requirements [ 58 ]. Travnickova et al report that melanoma persister cells originate from the primary tumor and that they contribute to cancer recurrence and drug resistance [ 59 ].…”

“…Travnickova et al report that melanoma persister cells originate from the primary tumor and that they contribute to cancer recurrence and drug resistance [ 59 ]. Melanoma is thought to be a chemotherapy-resistant cancer, and this resistance could be attributed to persister cells [ 58 , 59 ]. The further study of persister cells could help develop novel cancer therapeutic strategies.…”

“…Another important factor involved in melanomagenesis is persister cells. While some studies report that persister cells could be induced by chemotherapy [ 58 ], other studies attest that melanoma persister cells originate from the primary tumor and that they contribute to cancer recurrence and drug resistance [ 59 ]. These cells go through metabolic alteration to improve the survival of tumoral cells, sustain cell proliferation, avoid the action of drugs, and fulfill energy requirements [ 58 ].…”