Domestic medical staff identified the regulatory mechanism of innate immunity-derived proteins that promote cancer cell proliferation, growth, and survival.
A research team led by Professor Joon-Young Seo of the Department of Biomedical Sciences at Yonsei University College of Medicine announced on the 16th that they have identified the cancer metabolism control function and mechanism of action of biperin, a protein expressed by interferon known to cause anticancer immunity.
In the process of forming cancer tissue, cancer cells, unlike normal cells, have characteristics of changing metabolism so that they can proliferate, grow, metastasize, and survive even under adverse conditions such as nutrient deficiency and limited oxygen.
Cancer metabolism is known to be regulated through the PI3K/AKT pathway, but it is difficult to determine this as a mechanism that induces typical metabolic changes in cancer cells.
Cancer cells are exposed to cytokines secreted by various cells, including surrounding immune cells. Recently, the JAK/STAT pathway activated by interferon, known as a pleiotropic cytokine that induces an anticancer immune response, has also been reported to be involved in the regulation of cancer metabolism. However, the clear mechanism of action for this has not been elucidated.
The research team studied the cancer metabolism control function and mechanism of action of ‘Viperin’, one of the interferon-inducing proteins.
As a result, biperin expression was high in cancer tissues of patients with stomach cancer (288), lung cancer (230), breast cancer (1,981), kidney cancer (443), pancreatic cancer (184), and brain cancer (206). It was confirmed that the higher the expression level, the lower the survival rate of cancer patients.
To confirm the metabolic control function of biperin in cancer cells, the research team created and analyzed cancer cell lines that suppressed or highly expressed biperin.
As a result of the analysis, biperin was found to be expressed not only by interferon, but also by lack of oxygen and nutrient deficiency in the cancer microenvironment, promoting cancer cell energy metabolism and fatty acid synthesis, enabling cancer cells to proliferate and survive.
In particular, it has been confirmed that biperin is expressed in cancer stem cells that can differentiate into various cancer cells that are resistant to anticancer drugs, promoting metabolic changes and improving the characteristics of cancer stem cells.
This function of biperin has been shown to promote tumor growth in xenograft mouse experimental models.
Professor Seo said, “We have identified a new mechanism in which biferin protein expressed by interferon, which is known to cause anti-cancer immunity, regulates cancer stem cells and cancer cell metabolism to promote cancer proliferation, growth, and survival.” It is expected that it will be possible to overcome this problem and develop a treatment targeting cancer metabolism.”
The study results were published in the latest issue of the Journal of Clinical Investigation, an international academic journal.
