In APCmin mice, a model prone to intestinal and mammary cancer due to a non-sense mutation in an allele of the adenomatous polyposis coli (APC) gene, loss of NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) resulted in histone hyperacetylation, increased the abundance of intestinal stem cells (ISCs) and enhanced the tumor-initiating potential. The gene discussed is APC; the disease is breast cancer.