Fatty acid oxidation supports melanoma cell migration through autophagy regulation

Metastasis is one of the most malignant characteristics of cancer cells, in which metabolic reprogram-ming is crucial for promoting and sustaining multi-steps of metastasis, including invasion, migration and infiltration. Recently, it has been shown that melanoma cells undergo a metabolic switching toward the upregulation of fatty acid oxidation (FAO) during metastasis. However, the underlying mechanisms by which FAO contributes to metastasis of melanoma cells remain obscure. Here, we report that FAO contributes to melanoma cell migration and invasion by regulating the formation of autophagosomes. Pharmacological or genetic inhibition of FAO impairs migration of melanoma cells, which seems not to be linked to energy production or redox homeostasis. Importantly, we reveal that acetyl-CoA production by FAO contributes to melanoma cell migration through autophagy regulation. Mechanistically, FAO inhi-bition results in increased autophagosome formation, which suppresses migration and invasion prop-erties of melanoma cells. Our results underscore the crucial role of FAO in melanoma cell migration and support the potential therapeutic relevance of modulating cellular acetyl-CoA levels to inhibit cancer metastasis.& COPY; 2023 Elsevier Inc. All rights reserved.

Automated summary

Metastasis is a malignant characteristic of cancer cells. Melanoma cells undergo metabolic reprogramming during metastasis, specifically upregulation of fatty acid oxidation (FAO). Inhibition of FAO impairs migration of melanoma cells by regulating autophagosome formation. FAO inhibition increases autophagosome formation and suppresses migration and invasion properties of melanoma cells. Modulating cellular acetyl-CoA levels may be a potential therapeutic strategy for inhibiting cancer metastasis.