Exploring the Role of Citrate Transport Pathway in Liver Cancer Growth

Understudied gene provides insight into how liver cancer cells gain the nutrition necessary to proliferate.

Scientists have identified a gene that may influence hepatoma cell proliferation and play a key role in the progression of liver cancer.

In a study published in the Journal of Biological Chemistry, investigators sought to determine whether the sodium-coupled citrate transporter, called solute carrier family 13 members 5 (SLC13A5), regulated hepatic energy homeostasis and proliferation of hepatoma cells.

“The liver is one of the most busy, active organs in the body,” said Hongbing Wang.

Typically, it requires a lot of energy, and liver cancer seems to be one of the few cancer types with a rise in incidence, according to the study authors.

SLC13A5 produces a protein that transports citrate into cells. Although the gene is expressed primarily in the liver, little research has been done surrounding SLC13A5.

“If you search for SLC13A5 in PubMed—–I searched this morning––there are 54 publications, which is not a whole lot,” Wang said.

Most research on SLC13A5 has focused on its role in diabetes and obesity, which has shown knocking out the gene in mice prevents high-fat diet-induced obesity, according to the study.

The authors hypothesized that because SLC13A5 plays a role in homeostasis and energy balance in obesity, it could play a role in energy needed by liver cancer cells.

For the study, investigators used RNA interference to suppress the production of SLC13A5 in 2 human hepatocellular carcinoma lines. The findings showed the growth and division of the liver cancer cells significantly slowed.

When the cells were injected into mice, the cells with suppressed SLC13A5 formed barely discernable tumors compared with the cancer cells not manipulated.

The scientists believed the extracellular citrate used by the SLC13A5 protein is required for fatty acid synthesis in the liver cancer cells.

Although the preliminary findings show promise, the authors said comparing SLC13A5 activity in healthy and cancerous human liver tissue is needed.