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A single mutation can drive stem cells to tumour formation

No. 37c2 | 10/08/2015

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. 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".


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

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.


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