Author response: Repurposing of KLF5 activates a cell cycle signature during the progression from a precursor state to oesophageal adenocarcinoma

Le résumé fourni par la source

Acid fluids present in the gut can sometimes ‘go up’ and damage the oesophagus, the pipe that connects the mouth and the stomach. As a result, a small number of individuals can develop Barrett’s oesophagus, a condition where cells in the lining of the lower oesophagus show abnormal shapes. In certain patients, these cells then become cancerous, but exactly how this happens is unknown. This lack of understanding contributes to late diagnoses, limited treatment and low survival rates. Many cancers feature ‘signature’ mutations in a set of genes that controls how a cell can multiply. Yet, in the case of cancers of the lower oesophagus, known genetic changes have had a limited impact on our understanding of the emergence of the disease. Here, Rogerson et al. focused instead on non-genetic changes and studied transcription factors, the proteins that bind to regulatory regions of the DNA to switch genes on and off. A close inspection of cancer cells in the lower oesophagus revealed that, in that state, a transcription factor called KLF5 controls the abnormal activation of genes involved in cell growth. This is linked to the transcription factor adopting a different pattern of binding onto regulatory regions in diseased cells. Crucially, when the cell growth genes regulated by KLF5 are activated, patients have lower survival rates. Further work is now required to examine whether this finding could help to identify patients who are most at risk from developing cancer. More broadly, the results from the work by Rogerson et al. demonstrate how transcription factors can be repurposed in a disease context.

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