Many patients with cancers die as a result of metastasis, a process whereby the cancer spreads from the primary organ to other organs around the body.

Normally, the sodium leak channel non-selective protein (NALCN) is responsible for maintaining resting charges of cell membranes in excitable tissues, including respiration and circadian rhythms.

In this study, scientists uncovered the role of NALCN in excitable tissues such as skeletal, smooth, and cardiac muscle cells. They found that NALCN regulates the release of malignant and normal epithelial cells—a type of cell that covers the inside and outside surfaces of the body—into the blood. NALCN also regulates the trafficking of both malignant and normal epithelial cells to distant sites where they form metastatic cancers or apparently normal tissues, respectively.

In experiments with mice, researchers found that deleting NALCN from gastric, intestinal, or pancreatic adenocarcinomas—a type of malignant epithelial cancer— not only did not change the incidence of the tumor, but also markedly increased metastasis and the number of circulating tumor cells. Blocking NALCN channels also triggered more metastasis to occur. Deleting NALCN from mice that did not have cancerous mutations and never developed cancer triggered shedding of epithelial cells into the blood at similar levels to a cancer-bearing animal.

In all these cases, the cells trafficked to distant organs to form normal structures. Contrary to previous thought, NALCN regulates cell dissemination from solid tissues independent of cancer and the formation of the primary tumor.

“We are developing a clearer picture on the processes that govern how cancer cells spread,” said Gilbertson.

“We can now consider whether there are likely existing drugs which could be repurposed to prevent this mechanism from triggering cancer spreading in patients,” he added.