Fig. 7 | Oncogene

Fig. 7

From: Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma

Fig. 7

TERT offsets oxidative stress in NRAS-mutant melanoma. TERT is required for telomere integrity. Genetic silencing of TERT or pharmacological induction of telomere uncapping due to incorporation of the nucleoside analog 6-thio-dG triggers rapid telomere-induced foci (TIF) coupled to global DNA damage and increased production of ROS. Enhanced ROS levels prompts the activation of a ROS-scavenging adaptive response, mediated mainly by SOD2, which re-establishes steady levels of ROS and offsets oxidative stress. Treatment of NRAS-mutant melanoma cells with Gamitrinib, a mitochondrial disrupting agent, attenuates SOD2 levels impairing its ability to effectively restore redox balance, resulting in toxic levels of ROS and tumor cell death

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