Researchers from the Cancer Research UK Manchester Institute have shown that a mutant gene is linked to the formation of cell-in-cell structures.

They investigated the role played by the p53 gene in a process known as entotic engulfment, where one viable cell exists within the membrane of another, in a type of lung cancer. Such cell-in-cell (CIC) structures have been observed in several different cancers, including breast, lung, endometrial, pancreatic, skin and oral cancer. It is thought that they could have a role in tumour growth.

The team, involving scientists from Leicester, London, Glasgow and Manchester, has looked at CIC formation in lung adenocarcinoma, and in particular the effect of mutations in p53.

Dr Patricia Muller, who heads the Tumour Suppressors group at the CRUK Manchester Institute and is lead author on the paper, said: “Although CIC structures have been described in various tumour samples, we still know very little about their relevance in cancer growth.”

They found that there was a strong association between the frequency of CIC and the expression of mutant forms of p53. In their laboratory experiments, they showed that mutant p53 encourages the cellular engulfment process. Crucially they also observed that these mutant p53 cells survive and are able to overcome failures in cell division, resulting in cells with more than one nucleus and the production of extra daughter cells.

Dr Muller added: “We think that this combination of cellular engulfment and mutant p53 might drive abnormal cell division and lead to genomic heterogeneity. Understanding the mechanisms behind this could help us control the genetic evolution that we see in cancer.”

Paper entitled "Genomic instability in mutant p53 cancer cells upon entotic engulfment" Mackay HL, Moore D, Hall C, Birkbak NJ, Jamal-Hanjani M, Karim SA, Phatak VM, Piñon L, Morton JP, Swanton C, Le Quesne J, Muller PAJ. (2018) Nature Communications.