A Single Mutation Can Drive Stem Cells to Tumour Formation
19 August 2015
Scientists study process in the fruit fly Drosophila
Errors in the genome of stem cells often lead to cancer. This is especially true when the mutation inhibits differentiation of stem cells into mature cells. Researchers working with Prof. Dr. Bruce Edgar analysed this process in the fruit fly Drosophila. The studies were conducted within the DKFZ-ZMBH Alliance, the strategic cooperation between the German Cancer Research Center (DKFZ) and the Center for Molecular Biology of Heidelberg University (ZMBH). The results have been published in the journal “Nature Cell Biology”.
The scientists investigated tumours generated by intestinal stem cells. In these stem cells differentiation was blocked by suppressing the so-called Notch-signalling pathway. Prof. Edgar and colleagues found that mutated intestinal stem cells generated tumours only when the epithelial cells of the gut were stressed e.g. by an infection. Stress signalling resulted in elevated division rates of stem cells. On achieving a critical mass the tumours displaced the surrounding healthy gut cells thereby causing their detachement and finally death from apoptosis. The loss of gut epithelial integrity caused the underlying gut cells to release stress factors which further triggered tumour growth. Under normal conditions, these stress signals ensure daily regeneration of the gut epithelium. They trigger cell divisions of intestinal stem cells in the stem cell niche in order to produce new cells to maintain the gut epithelium.
The research has demonstrated that the mutated intestinal stem cells generated huge tumours in the flies without any additional genetic mutations. The scientists were caught by surprise because it is commonly believed that several genetic alterations are crucial for tumour development. “Niche-derived stress signals seem to be essential for differentiation-defective stem cells to progress to tumors,” says Bruce Edgar, researcher at both ZMBH and DKFZ.
Scientists of the Fred Hutchinson Cancer Research Center in Seattle (USA) also participated in the studies.
P.H. Patel, D. Dutta and B.A. Edgar: Niche appropriation by Drosophila intestinal stem cell tumours. Nature Cell Biology (3 August 2015), doi: 10.1038/ncb3214