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Cancer-linked protein helps control fate of intestinal stem cells

2015-03-09
(Press-News.org) HEIDELBERG, 10 March 2015 - An international group of researchers has shown that a regulatory protein involved in controlling how cancer spreads through the body also influences the fate of stem cells in the intestine of mice. The results, which are published in The EMBO Journal, show that the Snai1 protein plays an important role in deciding the fate of intestinal stem cells and the different functions that these cells can adopt.

"Our results show that Snai1 is a key regulator of crypt base columnar cells, a type of stem cell found in the invaginations or crypts that exist at the base of the many villi found in the intestine," remarked Helen E. Abud, Associate Professor at Monash University and one of the lead authors of the study. "The Snai1 protein has important roles in regulating how these stem cells survive in the intestine, the way in which they proliferate, and also their final fate."

It has been known for some time that different Snai proteins are crucial regulators of the way in which epithelial cells in the intestine give rise to migratory and invasive stem cells that help spread cancer in mice and humans. However the regular day-to-day role of these proteins has been less clear.

The proliferation of intestinal stem cells was compromised when the activity of Snai1 protein was reduced in the epithelial layer that forms the lining of the mouse intestine. Fewer crypt base columnar stem cells were generated. Instead the differentiation of the epithelial stem cells shifted towards cells that adopt secretory roles in the intestine (secretory endocrine and Paneth cells). Depletion of Snai1 also impaired the regeneration of the intestinal epithelium following damage induced by radiation.

"Snai1 acts like a master switch that carefully fine tunes the fate of stem cells in the crypts of the intestine," says Gary Hime, Associate Professor at Melbourne University and one of the lead authors of the paper. "When it is working properly, it orchestrates the regular differentiation and development of the stem cells into the cell types needed by the body. When it goes awry, it enhances the survival of invasive cells, promotes their migration to other tissues and enhances the propagation of tumours. We hope that by studying this balancing act in more detail that we will be able to identify possible intervention points that may prevent the changes associated with the development and spread of cancer in the intestine."

INFORMATION:

Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium

Katja Horvay, Thierry Jardé, Franca Casagranda, Victoria M. Perreau, Katharina Haigh, Christian M Nefzger, Reyhan Akhtar, Thomas Gridley, Geert Berx, Jody J. Haigh, Nick Barker, Jose M. Polo, Gary R. Hime and Helen E. Abud

The paper will be available at 12.00 Central European Time at emboj.embopress.org. For further information on The EMBO Journal please consult emboj.embopress.org

Media Contacts

Barry Whyte
Head | Public Relations and Communications
barry.whyte@embo.org

Thomas Schwarz-Romond
Senior Editor, The EMBO Journal
Tel: +49 6221 8891 407
schwarzr@embo.org

About EMBO EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.

EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe. For more information: http://www.embo.org



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[Press-News.org] Cancer-linked protein helps control fate of intestinal stem cells