Cancer cells fight for their footing by using an ageing gene

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.

Flanagan DJ, Pentinmikko N, Luopajärvi K, Willis NJ, Gilroy K, Raven AP, Mcgarry L, Englund JI, Webb AT, Scharaw S, Nasreddin N, Hodder MC, Ridgway RA, Minnee E, Sphyris N, Gilchrist E, Najumudeen AK, Romagnolo B, Perret C, Williams AC, Clevers H, Nummela P, Lähde M, Alitalo K, Hietakangas V, Hedley A, Clark W, Nixon C, Kirschner K, Jones EY, Ristimäki A, Leedham SJ, Fish PV, Vincent JP, Katajisto P, Sansom OJ.
NOTUM from Apc-mutant cells biases clonal competition to initiate cancer.
Nature. 2021 Jun 2. doi: 10.1038/s41586-021-03525-z

Most Popular Now

Therapy using dual immune system cells effectively…

A newly developed immunotherapy that simultaneously uses modified immune-fighting cells to home in on and attack two antigens, or foreign substances, on cancer cells was ...

How to develop new drugs based on merged datasets

Polymorphs are molecules that have different molecular packing arrangements despite identical chemical compositions. In a recent paper, researchers at GlaxoSmithKline (GS...

New drug combination effective against SARS-CoV-2 …

More countries with greater resources are opening up for a more normal life. But COVID-19 and the SARS-CoV-2 virus are still a significant threat in large parts of the wo...

Cleveland Clinic study suggests steroid nasal spra…

A recent Cleveland Clinic study found that patients who regularly use steroid nasal sprays are less likely to develop severe COVID-19-related disease, including a 20 to 2...

Sanofi to focus its COVID-19 development efforts o…

Recent positive interim results of Sanofi's mRNA-based COVID-19 vaccine candidate Phase 1/2 study confirm the company's platform robust capabilities and strategy in mRNA...

Discovery of mechanics of drug targets for COVID-1…

A team of international researchers, including McGill Professor Stéphane Laporte, have discovered the working mechanism of potential drug targets for various diseases suc...

Phase II/III trial shows Ronapreve™ (casirivimab a…

Roche (SIX: RO, ROG; OTCQX: RHHBY) today confirmed positive data from the phase II/III 2066 study, investigating Ronapreve™ (casirivimab and imdevimab) in patients hospit...

Pfizer and BioNTech receive first U.S. FDA Emergen…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced that the U.S. Food and Drug Administration (FDA) has authorized for emergency use a booster dose of the P...

AZD7442 request for Emergency Use Authorization fo…

AstraZeneca has submitted a request to the US Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA) for AZD7442, its long-acting antibody (LAAB) com...

Pfizer and BioNTech receive CHMP positive opinion …

Pfizer Inc. (NYSE: PFE, "Pfizer") and BioNTech SE (Nasdaq: BNTX, "BioNTech") today announced that the Committee for Medicinal Products for Human Use (CHMP) of the Europea...

GSK welcomes WHO recommendation for broad roll-out…

GlaxoSmithKline (GSK) plc welcomes and applauds the WHO recommendation for the broader deployment of GSK's RTS,S malaria vaccine to reduce childhood illness and deaths fr...

Boehringer Ingelheim acquires Abexxa Biologics to …

Boehringer Ingelheim announced the acquisition of Abexxa Biologics Inc., a biopharmaceutical company taking a new approach in the fields of immuno-oncology and oncology r...