Different hallmarks of cancer exist, and the glycolytic switch, which allows tumor cells to increase aerobic glycolysis to cope with their metabolic needs, seems to be crucial for cancer cell survival and proliferation. A new study shows that a molecule involved in glucose homeostasis acts as a tumor suppressor by repressing this switch independently of any oncogene (Cell 151, 1185–1199, 2012).

Carlos Sebastian et al. found that lack of sirtuin 6 (SIRT6), a protein involved in stress resistance, genomic instability and metabolic homeostasis, renders cells tumorigenic, even when the cells are not transformed. The tumor-suppressor effect of SIRT6 resulted from the inhibition of aerobic glycolysis, which was enhanced in tumors derived from Sirt6-deficient cells. The promotion of cancer initiation and progression in the absence of SIRT6 was independent of any oncogenic pathway and was suppressed upon inhibition of glycolysis, supporting the idea that this metabolic reprogramming drives tumor growth. A mouse model of colon carcinoma confirmed that deletion of Sirt6 in the intestine increased malignancy, and, in human colon cancers, low amounts of SIRT6 correlated with shorter time to relapse.

As SIRT6 was also found to regulate ribosome biosynthesis through co-repression of MYC activity, SIRT6 may be a metabolic node that ultimately controls tumor cell replication and growth in the absence of any other oncogenic event.