New protein linked to breast cancer progression discovered

Researchers from the Johns Hopkins University found how some tumours get the tools they need to metastasise.

"We've identified a protein that wasn't known before to be involved in breast cancer progression," said researcher Gregg Semenza.

"The protein JMJD2C is the key that opens up a whole suite of genes needed for tumours to grow and metastasise, so it represents a potential target for cancer drug development," Semenza said in a statement.

Researchers traced the activity of HIF-1, a protein known to switch on hundreds of genes involved in development, red blood cell production, and metabolism in normal cells.

Previous studies had shown that HIF-1 could also be hijacked to switch on genes needed to make breast tumours more malignant.

To learn more about how HIF-1 works, the researchers tested a range of human proteins to see whether they would interact with HIF-1.

They then sifted through the 200 resulting hits, looking for proteins involved in chemical changes to sections of DNA that determine whether or not the genes they contain are available for use.

"In order for HIF-1 to switch genes on, they have to be available, but many of the genes HIF-1 activates are normally locked down in mature cells. So we thought HIF-1 must have a partner that can do the unlocking. That partner turned out to be JMJD2C," said researcher Weibo Luo.

Researchers found that HIF-1 switches on the JMJD2C gene, stimulating production of the protein. HIF-1's presence also enables JMJD2C to bind to DNA at other HIF-1 target genes, then loosen those DNA sections, enabling more HIF-1 to bind to the same sites and activate the target genes.

To test the implications of their discovery, the research team injected mice with breast cancer cells in which the JMJD2C protein was not produced.

Tumours with depleted JMJD2C were much less likely to grow and metastasise to the lungs, confirming the protein's role in breast cancer progression, Luo said.

"Active HIF proteins have been found in many types of tumours, so the implications of this finding go beyond breast cancer," Luo said.

"JMJD2C is both an important piece of the puzzle of how tumors metastasise, and a potential target for anti-cancer therapy," Luo said.

The study was published in the Proceedings of the National Academy of Sciences.