Columbia researchers map out calcium-moving proteins associated with cancer

A recennt study by researchers at Columbia University describes a newly understood way that calcium gets into the human body. The channel is directly related to the aggressiveness levels of certain types of cancer, so understanding it better could help physicians find new ways to fight cancer.

The channel is a protein called TRPV6, and according to the study authors, it is one of two such proteins that specialize in introducing calcium into the body through pores on the skin. The existence of TRPV6 is important to normal bodily functions, because stable calcium levels are necessary for health.

For example, the researchers found that impairing calcium uptake through the TRPV6 channel in rats led to low body weight, infertility and skin issues. In humans, faulty TRPV6 proteins can mean kidney and digestive diseases. Too much of the protein is associated with cancer.

To better understand its function in humans, the researchers, led by Alexander Sobolevsky, mapped out the crystal structure of the TRPV6 in rats. According to the study, published in Nature, researchers crystalized the protein and found “the best crystals of TRPV6cryst diffracted to 3.25 Å resolution.” They used molecular replacement and an electron density map to get a 3D picture of the protein.

That model helped them understand what was happening with the protein inside human skin cells as calcium moved from outside the human body to inside. According to a statement by Columbia University Medical Center, the reason calcium molecules use the TRPV6 protein to move into a person is because the calcium molecules are positively charged and the TRPV6 molecules are negatively charged, at least on the surface of the pores on the skin. The two molecules are attracted to one another, and the TRPV6 proteins continue to pass the calcium through the skin cells and into the body.

Understanding the mechanism for how the proteins work could help physicians understand a way to manipulate them when they don’t work, including when their malfunction causes cancer.

“In future, we could use this model to design drugs that can target some types of tumor cells by plugging up TRP channels on their surfaces,” Sobolevsky said in the statement.