Scientists have found a colorectal cancer suppressor protein

Sofia Dolotovskaya, N+1

An international team of scientists has shown that a protein from the class of Nod-like receptors is able to suppress the development of colon and rectal cancer in mice. The article was published in the journal Nature (Karki et al., NLRC3 is an inhibitory sensor of PI3K–mTOR pathways in cancer).

Colon and rectal cancer, or colorectal cancer, is the third most common malignant neoplasm in the world, accounting for about 10 percent of cases of all oncological diseases. Previous studies have shown that the expression of the Nod-like receptor protein type 3 (NLRC3) gene is greatly reduced in this disease. NLRC3 protein belongs to the class of Nod-like receptors – intracellular sensor proteins that play an important role in immune processes, recognizing pathogen molecules, and are also involved in the regulation of intestinal homeostasis. However, the role of NLRC3 in the development of colorectal cancer has remained unclear until now.

The authors of the new article showed that in mice with colorectal cancer, pharmacological suppression of NLRC3 activity leads to a strong increase in the frequency of colitis (inflammation of the colon mucosa) and the formation of colorectal tumors. The most noticeable effect of NLRC3 was in enterocytes (epithelial intestinal cells). The increased expression of NLRC3 in enterocytes suppressed the activation of the mammalian rapamycin target signaling pathway (mTOR), the most important regulator of cell growth. Inhibition of the mTOR signaling pathway, in turn, occurred due to the binding of NLRC3 to phosphoinositide-3-kinase (PI3K) – a protein that triggers the activation of the mTOR pathway through a chain of molecular cascades. Since the PI3K/AKT/mTOR signaling pathway is activated at the early stages of tumor formation, suppression of its activation caused a strong slowdown in tumor cell division. NLRC3 thus acted as a regulator of the mTOR signaling pathway, suppressing abnormal cell growth.

The PI3K/AKT/mTOR signaling pathway regulates cell division, inflammation, and immune responses. Since there is an increased activity of this pathway in many malignant neoplasms, scientists have long considered it as a target for tumor therapy. As the authors conclude, the results obtained will allow further use of the NLRC3 protein to suppress tumor growth. To do this, scientists will need to find a way to stimulate its synthesis.

Portal "Eternal youth" http://vechnayamolodost.ru  15.12.2016