Lund researchers find out how E. coli bacteria target and reduce MYC oncogene

Scientists at Lund University have discovered how E. coli bacteria target and reduce the well-known oncogene MYC, which is involved in many types of cancer. The study is now published in Nature’s biotechnology.

Cancer cells grow too fast, surpass normal cells and spread to distant sites, where they cause metastases. Understanding what makes cancer cells so effective and threatening is crucial and stopping them has always been a goal for cancer research. Early studies identified so-called ” oncogenes ”; genes that normally control cell growth only when translocated may depend on the formation of cancer cells and the definition of their competitive advantage.

The pleiotropic transcription factor MYC has been described as ” the quintessential oncogene ” and is depressed in most human cancers. MYC targeting is therefore highly desirable. However, finding c-MYC inhibitors for therapeutic use has been difficult and MYC itself has long been seen as “undruggable”.

Researchers at Lund University have made the remarkable discovery that uropathogenic E. coli releases c-MYC proteins from infectious cells and tissues as a result of accelerated c-MYC protein depletion and accelerated MYC expression.

The discovery was made after it was observed that children with acute pyelonephritis have reduced MYC expression. By screening molecules released by the bacteria, Lon protease was identified as a major contaminant of MYC, with selectivity for MYC. The bacterial strategy was then translated into cancer treatment, showing obvious effects of Lon treatment in two different cancer models. Strong therapeutic effects on tumor growth and increased survival support the therapeutic potential of this molecule. Surprisingly, the Lon protease has been shown to mainly affect cells where MYC is overexpressed, suggesting a low level of toxicity. These results are now published in Nature’s biotechnology

The next step is to understand these “magic molecules” in more detail and develop the project for future clinical trials ”