04:45am Thursday 14 December 2017

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

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.


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