Aspartate’s surprising role in driving cancer

Malignant Cancerous Growth as growing dividing tumor cells and Malignancy disease spreading metastasized on an organ inside the human body as a 3D illustration.

Researchers from VIB-KU Leuven in Belgium have revealed new findings about the role that amino acid aspartate plays in cancer. Their study, published in Nature, suggests that high levels of aspartate cause diseased cells to metastasize, specifically in the lungs.

Prior scientific evidence has proven that more than half of patients with metastatic tumors develop lung metastases. To better understand the biology behind aggressive lung metastases, the investigators examined cellular gene expression.

What they found was evidence of alternative translation, in which a body’s genetic code has altered in such a way as to produce different proteins that trigger the cancerous cells to reproduce at higher rates in the lung ecosystem.

Ginevra Doglioni and Sarah-Maria Fendt(L to R): Ginevra Doglioni and Sarah-Maria Fendt, PhDVIBThe team discovered abnormally high concentrations of aspartate (a protein building block) in the lungs of mice and humans with metastatic breast cancer. Despite the increased levels, the researchers went on to realize that the amino acid wasn’t directly infiltrating the cancer cells, but rather initiating a modification process called hypusination.

More specifically, they found that aspartate signals an NMDA receptor in cancer cells (a cell surface protein) that activates eIF5A and starts the alternative translation program. Sarah-Maria Fendt, PhD, runs the Laboratory of Cellular Metabolism and Metabolic Regulation that completed the study. Ginevra Doglioni, PhD student at the Fendt lab, was first author of the study.

“This correlation emphasizes the relevance of the findings in a clinical context and suggests that aspartate signaling may be a common feature of cancer cells growing in the lung,” said Dr. Fendt, principal investigator at the VIB Center for Cancer Biology and associate professor of oncology at KU Leuven. “Moreover, there are drugs available to target the mechanism we identified, and thus, with further research, a translation toward a clinical setting might be possible.”

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