Asparagine Amino Acid Key To Breast Cancer Metastasis

An amino acid called asparagine is key to breast cancer’s spread, report researchers who found that by restricting it in mice, they could stop cancer cells from invading other parts of the body.

Most breast cancer patients don’t die from their primary tumor, but instead from metastasis, or the spread of cancer to the lungs, brain, bones, or other organs. To be able to spread, cancer cells first need to leave the original primary tumor, survive in the blood as “circulating tumor cells,” and then colonize other organs.

By finding a mechanism to block metastasis, researchers say they hope to save lives.

Blocking Asparagine

Scientists, led out of the Cancer Research UK Cambridge Institute, found that blocking the production of asparagine with a drug called L-asparaginase in mice with aggressive triple negative breast tumors, and putting them on a low-asparagine diet, greatly reduced the breast tumor’s ability to spread.

Asparagine is an amino acid — the building blocks that cells use to make proteins. While the body can make asparagine, it’s also found in our diet, with higher concentrations in some foods, including asparagus.

The mouse studies prompted researchers to examine data from breast cancer patients. These data indicated that the greater the ability of breast cancer cells to make asparagine, the more likely the tumor was to spread.

In several other cancer types, researchers found that the increased ability of tumor cells to make asparagine was associated with reduced survival.

Cancer Metabolism Intervention

Coauthor Lisa A. Carey said:

“It does highlight, again, the importance of cancer metabolism, and suggest that it may be an area of therapeutic intervention in the future. It’s not ready for clinical action today, but it’s a promising approach. We and many others are pursuing this cancer metabolism angle.”

Carey, professor in breast cancer research and physician-in-chief of the NC Cancer Hospital, offered a word of caution that more research needs to be done to evaluate diet restriction in cancer patients to restrict metastasis, adding there is a drug used to treat leukemia that uses asparagine-based metabolism as its target:

“We can potentially manage cancers better in the future if we really understand what nutrients they require. It’s important for us to understand how cancers grow, and how they feed themselves, and what they require in order to grow. That may be something they can modulate.”

The research was funded by Hope Funds For Cancer Research, Human Frontier Science Program, Susan G. Komen Foundation, NCI Breast SPORE program, Breast Cancer Research Foundation, Triple Negative Breast Cancer Foundation, the National Institutes of Health, the Institute of Cancer Research, CRUK Grand Challenge Award, Cancer Research UK, and the DOD BCRP.

Simon R. V. Knott, Elvin Wagenblast, Showkhin Khan, Sun Y. Kim, Mar Soto, Michel Wagner, Marc-Olivier Turgeon, Lisa Fish, Nicolas Erard, Annika L. Gable, Ashley R. Maceli, Steffen Dickopf, Evangelia K. Papachristou, Clive S. D’Santos, Lisa A. Carey, John E. Wilkinson, J. Chuck Harrell, Charles M. Perou, Hani Goodarzi, George Poulogiannis & Gregory J. Hannon
Asparagine bioavailability governs metastasis in a model of breast cancer
Nature volume 554, pages 378–381 (15 February 2018) doi:10.1038/nature25465