Uncoupling protein 2 is upregulated in melanoma cells and contributes to the activation of Akt/mTOR and ERK signaling

: The aim of the present study was to characterize the expression of uncoupling protein 2 (UCP2) in melanoma and to study the potential mechanisms underlying the involvement of UCP2 in melanomagenesis using human melanoma cell lines. The expression of UCP2 was evaluated in specimens from normal control subjects, patients with compound nevus, and patients with cutaneous and mucosal melanoma. Stable knockdown of UCP2 was achieved in human melanoma cell lines, which were used to examine whether UCP2 knockdown affects the mitochondrial membrane potential and intracellular levels of ATP, reactive oxygen species and lactate. Cell proliferation, invasion, spheroid formation and cisplatin sensitivity were also evaluated in the UCP2 knockdown cells. Finally, the effects of UCP2 knockdown on the Akt/mammalian target of rapamycin (mTOR) and extracellular signal‑regulated kinase (ERK) pathways, which are important oncogenic pathways during melanomagenesis, were evaluated. Relatively high expression of UCP2 was detected in human melanoma specimens, which was correlated with Clark level and Breslow thickness. Knockdown of UCP2 suppressed cell proliferation, invasion and spheroid formation, and increased the sensitivity of melanoma cells to cisplatin. Furthermore, the UCP2 knockdown cells exhibited inhibition of Akt/mTOR signaling and ERK activation. Therefore, human melanoma tissues exhibit relatively high UCP2 expression, which may be implicated in the mechanisms underlying tumor progression. The potential role of UCP2 in melanomagenesis may involve enhancing the Akt/mTOR and mitogen‑activated protein kinase/ERK pathways.