A new study has found how a single cancer-causing gene mutation (in the Ras gene) can rapidly change normal cells and trigger an immune response that promotes cancer formation - all within just 24 hours. This may offer new ways to detect or prevent cancer before it becomes established. The body is made up of cells, with instructions on how to behave driven by segments of DNA called genes, inside them. Sometimes, this DNA changes - or mutates - and this can cause the cell to divide and grow uncontrollably, often, but not always, causing cancer. It is not known how the normal functioning cells surrounding these emerging mutant cells and host immune cells respond, and whether they promote or suppress the mutant cell to become cancerous.The Feng lab (IRR and Institute of Genetics and Cancer) and colleagues used zebrafish - whose transparency allows scientists to watch cells develop in real-time - to study what happens right after mutating a gene called Ras. Ras is one of the most commonly mutated genes in human cancers. Surprisingly, they found that this single genetic change was enough to make some skin cells “flip” into a more flexible, stem cell–like state, a key early step for the progression of cancer. From normal cell to “shape-shifter” cellThe scientists observed that when the mutant Ras gene was mutated, a subset of skin cells began losing their usual identity and started acting more like stem cells, as many of their genes had been switched on. Some of these cells then started to show features of early cancer cells, becoming more mobile and invasive. The researchers call these cells PNC-3, and they think these are the ones most likely to eventually start tumours.Importantly, the study showed that Ras mutation alone can trigger these dangerous changes, but only in certain cell types, especially stem-like cells deep in the skin. This supports the idea that cancer often begins in long-lived stem cells. Tricking the immune systemThe researchers also discovered that the newly transformed subset of cells send out chemical signals that attract immune cells called neutrophils to the area. Instead of attacking the abnormal mutant cells, these neutrophils promoted further cell growth, creating a feedback loop that promoted tumour development. Blocking one of the main signaling pathways (the Il8–Cxcr2 axis) reduced this effect but didn’t completely stop it, suggesting other signals are also involved. Here we identify key features of Ras-mutated skin cells that are more likely to drive cancer formation and have identified candidate signals these cells send out to drive a tumour promoting immune response. This is useful for future development of cancer prevention and early detection strategies. Dr Yi Feng IRR and IGC Group Leader Neutrophils (magenta) remain outside normal skin tissue (left) but are recruited to Ras-mutated cells within the skin (right), where they promote mutant cell growth rather than eliminating them. Why it mattersThe study shows that the very earliest steps in cancer initiation involves both genetic changes inside the cell and interactions with the immune system. These events happen surprisingly fast - within just a day of Ras mutation - and may offer new ways to detect or prevent cancer before it becomes established.The researchers now want to study the required features of cells in the body that allow genes like RAS to drive the formation of tumours. They also want to further study the mechanism that regulates the interaction between tumour-initiating RAS skin cells and immune cells.This work was funded by Cancer Research UK, Wellcome Trust and UKRI Read the full article in Cell Reports Feng research labInstitute of Genetics and Cancer Tags CIR Publication date 28 Oct, 2025
