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Cancer cells fight for their footing by using an aging gene

June 15, 2021
University of Helsinki
New results allow the development of novel therapies for hereditary forms of intestinal cancer.

Researchers at the University of Helsinki and the Beatson Institute for Cancer Research in Glasgow have discovered how mutated cells promote their chances to form cancer. Typically, the accumulation of harmful cells is prevented by active competition between multiple stem cells in intestinal glands, called crypts.

"The functioning of intestinal stem cells relies on growth factors, named Wnts, produced by the surrounding environment. Intestinal cancers typically originate from stem cells where mutations allow growth independent of these factors. When we removed a gene called Notum, which renders Wnts inactive, from mutated stem cells, the number of precancerous adenomas in the intestine was greatly reduced. We found that mutated cells use this gene to block environmental factors critical to normal stem cells gaining advantage in competition," says Postdoctoral Researcher Nalle Pentinmikko.

The research group of Assistant Professor Pekka Katajisto at the Institute of Biotechnology of the University of Helsinki had already previously discovered that the same gene, also called an 'ageing gene', is expressed in normal tissue when we age, reducing the ability of stem cells to repair damage. The current study shows that mutated cells use the same gene in order to establish a permanent footing in the tissue.

"Mutated cells kind of hijack the ageing gene and use it against the healthy stem cells," Katajisto says.

The results from this study may lead to the development of new therapies, because the function of the enzyme encoded by the ageing gene can be blocked pharmacologically. The research group led by Katajisto has previously used a compound for this purpose in aged research animals to enhance the function of aged stem cells. In the current study, researchers used the same method to reduce the chance of mutated cells winning in competition. A three-week treatment reduced the number of adenomas in animal models.

"The results are promising and create a foundation for developing new therapies for patients predisposed to intestinal cancers. This research demonstrates that by enhancing the natural mechanisms of how tissues remove damaged cells, we could also reduce cancer risk in other tissues," Pekka Katajisto concludes.

Story Source:

Materials provided by University of Helsinki. Note: Content may be edited for style and length.

Journal Reference:

  1. Dustin J. Flanagan, Nalle Pentinmikko, Kalle Luopajärvi, Nicky J. Willis, Kathryn Gilroy, Alexander P. Raven, Lynn Mcgarry, Johanna I. Englund, Anna T. Webb, Sandra Scharaw, Nadia Nasreddin, Michael C. Hodder, Rachel A. Ridgway, Emma Minnee, Nathalie Sphyris, Ella Gilchrist, Arafath K. Najumudeen, Beatrice Romagnolo, Christine Perret, Ann C. Williams, Hans Clevers, Pirjo Nummela, Marianne Lähde, Kari Alitalo, Ville Hietakangas, Ann Hedley, William Clark, Colin Nixon, Kristina Kirschner, E. Yvonne Jones, Ari Ristimäki, Simon J. Leedham, Paul V. Fish, Jean-Paul Vincent, Pekka Katajisto, Owen J. Sansom. NOTUM from Apc-mutant cells biases clonal competition to initiate cancer. Nature, 2021; DOI: 10.1038/s41586-021-03525-z

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University of Helsinki. "Cancer cells fight for their footing by using an aging gene." ScienceDaily. ScienceDaily, 15 June 2021. <>.
University of Helsinki. (2021, June 15). Cancer cells fight for their footing by using an aging gene. ScienceDaily. Retrieved April 12, 2024 from
University of Helsinki. "Cancer cells fight for their footing by using an aging gene." ScienceDaily. (accessed April 12, 2024).

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