Researchers at IRB discover a key regulator of colon cancer

A team headed by Angel R. Nebreda at the Institute for Research in Biomedicine (IRB) identifies a dual role of the p38 protein in colon cancer. The study demonstrates that, on the one hand, p38 is important for the optimal maintenance of the epithelial barrier that protects the intestine against toxic agents, thus contributing to decreased tumour development. Intriguingly, on the other hand, once a tumour has formed, p38 is required for the survival and proliferation of colon cancer cells, thus favouring tumour growth. The study is published today in Cancer Cell, a journal with one of the highest impact factors in cancer research.

p38 enhances the survival of colon cancer cells

The protein p38 is a member of the MAPK family - molecules that transmit signals from outside the cell inside, thus allowing an appropriate and dynamic cell response. This protein is expressed in all cells of the body and it performs highly diverse functions depending on the context and tissue involved. Nebreda's group at IRB focuses on the function of p38 in cancer. Their work describes the essential role of p38 in tumour progression for the first time in vivo. Furthermore, the scientists demonstrate that the treatment of mice with a p38 inhibitor previously used in clinical assays causes a considerable reduction in tumour size. The study provides useful information for clinicians and pharmaceutical companies about the role of p38 in the context of colon cancer. Colorectal cancer is now the second leading cause of cancer-related death in the world.

"p38 inhibitors may have clinical applications, but probably - and this forms part of the medicine of the future - these will be in combination with other drugs. We are trying to find out what p38 inhibitors should be combined with to make the tumour, which is now smaller, finally disappear," explains the Spanish scientist Nebreda, head of the Signalling and Cell Cycle Lab at IRB, BBVA Foundation Cancer Research Professor and ICREA research professor.

p38 suppresses pre-tumoral stages characterized by colon inflammation

The role of p38 in cancer is not clear cut. In this same study, Indian-born Jalaj Gupta who recently obtained his PhD in Nebreda's lab and is first author of the work, demonstrates that this same protein in a pre-tumoral context, favoured by inflammation of the colon - also known as colitis - impedes tumour development. It is well-known that patients with chronic inflammation of the intestine, such as that caused by Crohn's disease, have a greater incidence of colon tumours that the healthy population. In order to study the relationship between inflammation and cancer, Nebreda's team use mouse models that reproduce this inflammatory context. "Given that p38 regulates inflammation and also functions as a tumour suppressor in some mouse models, our study addressed how these two functions are integrated during the colon tumorigenesis associated with inflammation", says Gupta.