The role of FAMIN in cancer development

In the human body, many cells need to grow and divide quickly to fulfill their specific tasks. When this tightly regulated process occurs in an uncontrolled manner, cancer can develop. For this to happen, however, several mutations are necessary for the cell to e.g. evade from the immune system and to provide sufficient amounts of nutrients and energy to fuel the increased demand. While the evasion from the immune system is critical for tumor cells, unspecific inflammation leads to a stressful tissue environment and thus, can increase the risk for cancer development. These interplays underline the complex relationship between tumor development and immunity. Once cancer has developed, however, the increased energy demand is aided by increased metabolism of sugar that is provided via the blood. In addition, metabolism of fatty acids is also increased, resulting in an increased supply of adenosine triphosphate (ATP), the cells energy store. One approach, therefore, is to starve cancer cells to death instead of using classic chemotherapies with an increased occurrence of adverse events. As most tumors are recognized by the immune system, however, further knowledge on the specific demands of cancer cells is necessary to avoid collateral damage on other cell types. As there is insufficient knowledge available to date, further research is necessary in the field. In a recently published study, a new protein called FAMIN was discovered that plays a significant role in cell metabolism in many different cell types. The amount of protein produced within a cell is highest in macrophages, a specialized immune cell. In these cells, a reduction in the quantity of produced protein results in a reduction of approximately one third of the cells total ATP levels. In addition, the macrophages were impaired in their ability to clear pathogens. When closer investigating the mechanisms leading to these findings, the cause of these profound changes was a reduction in sugar as well as fatty acid metabolism. As the protein is not exclusively produced in macrophages, a lack or insufficient activity of FAMIN leads to an increased risk to develop chronic inflammatory bowel disease (Crohns disease) or an autoimmune disease (systemic juvenile idiopathic arthritis). As interference of protein expression might impair tumor growth by reduction of sugar as well as fatty acid metabolism, but does also change immune cell function, further research is necessary to investigate the interplay of both. Results from this project should help to tailor therapies to the patients needs in order to avoid adverse events resulting from unspecific therapies.

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