Expression data profile of A498 cells infected with E. coli 536 or PAI I delation mutant

MYC has been named the quintessential oncogene and is deregulated in the majority of human cancers. Still, finding c-MYC inhibitors for therapeutic use has been problematic and MYC itself has long been viewed as “undruggable”. Here we present a novel strategy for achieving c-MYC inhibition, involving specific bacterial effector molecules. We made the surprising observation that uropathogenic E. coli activate c-MYC degradation and attenuate MYC expression in host cells and tissues. We further identified effector molecules responsible for this effect. The bacterial Lon protease is shown to rapidly degrade c-MYC and therapeutic efficacy is demonstrated in bladder and colon cancer models. Long-term protection, defined by delayed tumor progression, increased survival and low toxicity further supports the therapeutic potential of Lon. These results suggest that bacteria have evolved strategies to control c-MYC tissue levels in the host, which can be exploited to target c-MYC therapeutically in different cancers. A498 kidney epithelial cells were infected with 10^5 CFU/ml of E. coli 536 or E. coli 536 PAI I deletion mutant for 4 hours. Cells with culture medium with PBS were used as a control. Isolated RNA was subjected to Affymetrix whole genome transcriptome analysis.