Researchers link new molecular culprit to breast cancer progression

November 25, 2012

(Phys.org)—Johns Hopkins researchers have uncovered a protein "partner" commonly used by breast cancer cells to unlock genes needed for spreading the disease around the body. A report on the discovery, published November 5 on the website of the Proceedings of the National Academy of Sciences, details how some tumors get the tools they need to metastasize.

"We've identified a protein that wasn't known before to be involved in breast cancer progression," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine at the Johns Hopkins University School of Medicine and director of the Vascular Program at Hopkins' Institute for . "The protein JMJD2C is the key that opens up a whole suite of genes needed for tumors to grow and metastasize, so it represents a potential target for ."

Semenza and his colleagues made their finding when they traced the activity of HIF-1, a protein known to switch on hundreds of genes involved in development, production, and metabolism in normal cells. Previous studies had shown that HIF-1 could also be hijacked to switch on genes needed to make more malignant.

Would-be tumor cells face a host of challenges as they make the transition from working with their host to working against it, such as the need to evade the immune system and to produce more cancer cells, explains Weibo Luo, Ph.D., an instructor in the Institute for Cell Engineering and Department of who led the project. All of these efforts require switching on the right genes for the job.

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," explains Luo. "So we thought HIF-1 must have a partner that can do the unlocking."

That partner turned out to be JMJD2C, Luo says. Delving deeper, the 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 in which the JMJD2C protein was not produced. Tumors with depleted JMJD2C were much less likely to grow and metastasize to the lungs, confirming the protein's role in breast , says Luo.

"Active HIF proteins have been found in many types of tumors, so the implications of this finding go beyond ," says Luo. "JMJD2C is both an important piece of the puzzle of how tumors metastasize, and a potential target for anti-cancer therapy."

Other authors of the research report are Ryan Chang, Jun Zhong, Ph.D., and Akhilesh Pandey, M.D., Ph.D., all of the Johns Hopkins University School of Medicine.

Explore further: Understanding cancer energetics

More information: www.pnas.org/content/early/201 … /1217394109.abstract

Related Stories

Understanding cancer energetics

June 4, 2011
(Medical Xpress) -- It's long been known that cancer cells eat a lot of sugar to stay alive. In fact, where normal, noncancerous cells generate energy from using some sugar and a lot of oxygen, cancerous cells use virtually ...

How breast cancer spreads: Researchers find key to lymph node metastasis in mice

September 10, 2012
The invasion of cancer cells into the lymph vessels that connect the breast to surrounding lymph nodes is the first step leading to the metastasis, or spread, of cancer throughout the body. Metastasis is the primary cause ...

Researchers discover how breast cancer spreads to lung

November 16, 2011
The spread of breast cancer is responsible for more than 90 percent of breast cancer deaths. Now, the process by which it spreads -- or metastasizes -- has been unraveled by researchers at Johns Hopkins.

Researchers link cell division and oxygen levels

June 11, 2011
Cells grow abundant when oxygen is available, and generally stop when it is scarce. Although this seems straightforward, no direct link ever has been established between the cellular machinery that senses oxygen and that ...

Recommended for you

Major study of genetics of breast cancer provides clues to mechanisms behind the disease

October 23, 2017
Seventy-two new genetic variants that contribute to the risk of developing breast cancer have been identified by a major international collaboration involving hundreds of researchers worldwide.

Microbiologists contribute to possible new anti-TB treatment path

October 23, 2017
As part of the long effort to improve treatment of tuberculosis (TB), microbiologists led by Yasu Morita at the University of Massachusetts Amherst report that they have for the first time characterized a protein involved ...

New study shows how cells can be led down non-cancer path

October 23, 2017
As cells with a propensity for cancer break down food for energy, they reach a fork in the road: They can either continue energy production as healthy cells, or shift to the energy production profile of cancer cells. In a ...

Proton therapy lowers treatment side effects in pediatric head and neck cancer patients

October 23, 2017
Pediatric patients with head and neck cancer can be treated with proton beam therapy (PBT) instead of traditional photon radiation, and it will result in similar outcomes with less impact on quality of life. Researchers from ...

Big Data shows how cancer interacts with its surroundings

October 23, 2017
By combining data from sources that at first seemed to be incompatible, UC San Francisco researchers have identified a molecular signature in tissue adjacent to tumors in eight of the most common cancers that suggests they ...

Symptom burden may increase hospital length of stay, readmission risk in advanced cancer

October 23, 2017
Hospitalized patients with advanced cancer who report more intense and numerous physical and psychological symptoms appear to be at risk for longer hospital stays and unplanned hospital readmissions. The report from a Massachusetts ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.