Acetate Metabolism in Thyroid Cancer Progression

In recent years, several studies have highlighted the ability of malignant cells to use acetate as an alternative energy and biosynthetic source to glucose. In this context, the present study aimed at characterizing the expression profile of genes involved in acetate metabolism in thyroid carcinomas. To this end, we analyzed molecular and clinical data from 496 papillary thyroid cancers (PTCs) and 59 normal thyroid tissues from The Cancer Genome Atlas (TGCA). In addition, we examined 57 PTCs and matched normal tissues, and six anaplastic thyroid carcinomas (ATCs) collected in our institutions, using real time RT-PCR. The results show a downregulation of ACSS1, ACSS2, ACACB, PDHA1, SLC16A3 and SLC16A7 genes in PTCs compared with normal tissues, some of which were significantly lower in BRAF-mutated tumors, the more aggressive tall cell variant, and larger and/or metastatic PTCs. Overall, these findings point to a reduction in mitochondrial oxidative pathways that was more evident in advanced or aggressive disease forms. In ATCs, ACSS2 was the only upregulated gene, suggesting further tumor adaptation to the metabolic stress of rapidly growing cancers. In conclusion, our study demonstrates a dysregulated expression pattern of multiple genes involved in acetate metabolism, which could be exploited for the development of new therapeutic strategies.