A single mutation can drive stem cells to tumour formation

This is especially true when the mutation inhibits differentiation of stem cells into mature cells. Bruce Edgar and colleagues from the Heidelberg DKFZ-ZMBH-Alliance analysed this process in the fruit fly Drosophila. The results have just been published in the journal “Nature Cell Biology”.

enlarged view © dkfz.de

Edgar, Patel and colleagues investigated tumours generated by intestinal stem cells. In these stem cells differentiation was blocked by suppressing the so-called Notch-signalling pathway. The researchers 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 mutated intestinal stem cells generated huge tumours in the flies without any additional genetic mutations. The scientists were caught by surprise because it is common 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,”  said Edgar.

*Deutsches Krebsforschungszentrum und Zentrum für molekulare Biologie der Universität Heidelberg

Parthive H. Patel, Devanjali Dutta and Bruce A. Edgar: Niche appropriation by Drosophila intestinal stem cell tumours. Nature Cell Biology 2015, DOI: 10.1038/ncb3214

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