A protein deficiency triggers colon cancer, according to a new Spanish study.

Colon cancer is the most commonly diagnosed cancer in the general Spanish population , according to data from the Spanish Association Against Cancer . According to available evidence, up to 80% of cases are related to various environmental or lifestyle factors , such as unhealthy diets, a sedentary lifestyle, obesity, and tobacco or alcohol consumption.

Now, a new study led by Nabil Djouder, head of the Growth Factors, Nutrients and Cancer Group at the Spanish National Cancer Research Centre (CNIO), has described a new molecular mechanism that could be involved in the formation of colorectal tumors and promote their progression toward more aggressive forms.

An antitumor protein that disappears

As these authors explain in an article published in the prestigious academic journal Nature Communications , to reach these conclusions, they conducted a series of studies on animal models (mice) in which they observed that a specific protein, called p53 , began to degrade in the early stages of tumor formation. This, they say, could lead to the development and development of cancer.

Indeed, other studies have already documented the antitumor function of the p53 protein : it is known to block cell division and contribute to cell destruction when they contain dangerous abnormalities, inhibiting the abnormal replication of damaged cells that gives rise to tumors. Conversely, the reduced presence of p53 that these researchers have novelly observed in colon cancer could increase the likelihood of uncontrolled cell growth.

Furthermore, this study also discovered another interesting mechanism: the relationship between p53 and another protein called URI , which was already known to be expressed (i.e., present) in other types of tumors. Specifically, the authors observed that as URI protein levels increased, p53 levels decreased.

A possible method to combat cancer

This is also the first time that the URI protein has been associated with colorectal tumors. As lead author Irene Herranz-Montoya explains in a statement published by the CNIO , "URI levels begin to rise very early on, leading to the formation of adenomas, an aberrant growth that does not yet constitute cancer, but it is at this stage that p53 begins to degrade."

In experiments conducted on mice, they found that eliminating the URI protein or increasing p53 levels in polyps, a type of precancerous lesion that appears in colon tissue, prevented them from transforming into tumors, and the mice with colorectal cancer lived longer.

"Our results," Herranz continues, "provide a more detailed understanding of how colorectal cancer evolves. If we focus on studying the colorectal mechanisms that cause p53 degradation, including the increase in URI, we could in the future intervene in the early stages of cancer and prevent its progression to more aggressive forms of the disease." Therefore, the team is now focusing on developing inhibitors of the URI protein.

Relationship with genetics and lifestyle

In this regard, the researchers have also identified that the level of URI protein expression is regulated by an oncogene called MYC, which had previously been identified as being involved in cell proliferation and the regulation of other key cancer genes. MYC activates URI expression, triggering the entire process these authors have described.

Furthermore, they say, this new mechanism could shed light on recent studies investigating possible causes of the rise in colon cancer cases in young adults and help better understand the relationship with environmental and lifestyle factors.

"My team had previously shown that URI expression is linked to certain environmental factors , such as poor diet, in both other cancers and bowel cancer. This suggests that URI and p53 degradation in the onset of colorectal cancer may be associated with these factors," explains Djouder.

Furthermore, this progressive decline in the p53 protein occurs independently of another previously known process : the loss of the TP53 gene (which encodes the p53 protein) in the late stages of colorectal cancer. In other words, both processes can occur and affect cancer development in parallel: in the early stages, protein degradation, and in more advanced or more aggressive stages (and even metastasis), gene loss.

All these findings have been further validated using human samples donated by the Ramón y Cajal Hospital Biobank , in collaboration with Cristian Perna, from patients with adenomas and advanced-stage colon cancer. They have also been complemented with data analyzed using bioinformatics methods.

References

AECC (2025). Colon cancer. Accessed online at https://www.contraelcancer.es/es/todo-sobre-cancer/tipos-cancer/cancer-colon on May 7, 2025.

Irene Herranz-Montoya, Mariana Angulo-Aguado, Cristian Perna, Sladjana Zagorac, Luis García-Jiménez, Solip Park & ​​Nabil Djouder. p53 protein degradation redefines the initiation mechanisms and drives transitional mutations in colorectal cancer. Nature Communications (2025). DOI: https://doi.org/10.1038/s41467-025-59282-4

CNIO (2025). Nature Communications. A molecular mechanism that triggers colon cancer has been discovered. Accessed online at https://www.cnio.es/noticias/descubierto-un-mecanismo-molecular-que-inicia-el-cancer-de-colon/

Do you want to receive the best content to take care of your health and feel good? Sign up for our free newsletter.