DTL promotes melanoma progression through rewiring cell glucose metabolism

Abstract

BACKGROUND: To investigate the role of DTL in the development of skin cutaneous melanoma (SKCM) and possible mechanisms. METHODS: We examined the expression of DTL in SKCM in The Cancer Genome Atlas (TCGA) and Oncomine database and analyzed the relationship between DTL expression and melanoma prognosis. Furthermore, we silenced the DTL gene by RNA interference in A375 cells and investigated the effect of DTL silencing on the biological function of melanoma cells. RESULTS: The expression of DTL in SKCM was upregulated in the tumor tissues compared with the paired normal tissues. Survival analysis showed that higher DTL expression in SKCM patients was associated with poor clinical outcome compared with the lower DTL expression group. Silencing of DTL in A375 cells significantly inhibited the melanoma cell growth and proliferation ability, and also significantly decreased the total glucose consumption and lactate production. Gene set enrichment analysis (GSEA) showed that MYC targets gene set pathway was highly enriched in the DTL high expression group. The expression levels of some MYC targets-related oncogenes, including c-MYC, HK1, HK2, PGK1, ENO1, LDHA, IDH1, ACLY, and HMGCR, were reduced in the A375 cells with knockdown DTL and upregulated in SKCM tissues with high DTL expression, and there was a positive correlation between them. CONCLUSIONS: An important role is played by DTL in promoting melanoma cell growth and glucose metabolism, possibly through activation of the MYC target pathway.