NVD-BM-mediated genetic biosensor triggers accumulation of 7-dehydrocholesterol and inhibits melanoma via Akt1/NF-ĸB signaling.

ABSTRACT: Aberrant activation of the cholesterol biosynthesis supports tumor cell growth. In recent years, significant progress has been made by targeting rate-limiting enzymes in cholesterol biosynthesis pathways to prevent carcinogenesis. However, precise mechanisms behind cholesterol degradation in cancer cells have not been comprehensively investigated. Here, we report that codon optimization of the orthologous cholesterol 7-desaturase, NVD-BM from Bombyx mori, significantly slowed melanoma cell proliferation and migration, and inhibited cancer cell engraftment in nude mice, by converting cholesterol to toxic 7-dehydrocholesterol. Based on these observations, we established a synthetic genetic circuit to induce melanoma cell regression by sensing tumor specific signals in melanoma cells.

SUBMITTER: Liu J 

PROVIDER: S-EPMC7425431 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature