PIONEERING research from the University of Maryland, Baltimore, Maryland, USA, has found a potential link between a relatively under-studied gene and liver cancer. The gene, named SLC13A5, is responsible for the production of a protein that transports citrate into various cells and is mainly expressed in the liver. Dr Hongbing Wang, University of Maryland, and his team, began research on the gene while comparing the metabolism of healthy and cancerous liver cells and the genes that may be important in the transition between the two.
Cancer cells proliferate uncontrollably and require large amounts of energy to do so. Potential therapy options may therefore involve interrupting the pathways that the cancer cells use to obtain this energy. The liver already requires high amounts of energy, which perhaps suggests that a specialised mechanism is involved in the formation of liver cancer. Previous studies have found that the SLC13A5 gene plays a part in obesity and diabetes development, with mice lacking the gene becoming immune to high-fat diet-induced obesity. Dr Wang and his team hypothesised that if this gene plays a role in energy homeostasis in obesity, perhaps it also plays a role in the energy requirements of liver cancer cells.
The study itself used a technique called RNA interference to limit the expression of SLC13A5, which hindered protein production, in cultures of two human hepatocellular carcinoma cell lines. This resulted in slowed growth and division of the cancerous liver cells, but not death. Similar results were seen when the cancerous liver cells were injected into mice with suppressed SLC13A5. The team suggested that the extracellular citrate taken up by the SLC13A5 protein is essential for fatty acid synthesis in cancerous liver cells. Interestingly, prostate cancer was unaffected by SLC13A5 suppression, as it is not expressed on the prostate, highlighting the differences in adaptations for energy acquisition between different cancer types.
The authors acknowledge that the results of the study are only an introduction to this novel research area, and further studies are required that directly compare SLC13A5 activity in healthy and cancerous human liver cells. Once these investigations have been performed, it may be possible to begin the formulation of a drug that targets the SLC13A5 protein pathway as a form of liver cancer therapy.