A new study has uncovered why the lungs are a frequent site of cancer metastasis, highlighting the role of aspartate in this process.
In a groundbreaking study published in the journal Nature, researchers have identified a crucial factor that makes the lung a frequent target for cancer metastasis.
The team, led by Sarah-Maria Fendt, principal Investigator at the VIB Center for Cancer Biology and professor of oncology at KU Leuven, Belgium, has discovered that aspartate, an amino acid, plays a significant role in this process, offering new insights that could lead to innovative therapeutic interventions.
Cancer metastasis to the lungs is a common occurrence, affecting over half of patients whose cancer spreads beyond the primary site.
This study sheds light on why the lungs are so susceptible to metastatic cancer cells. By investigating gene expression in cells from aggressive lung metastases, the researchers found evidence of an alternative “translation program.”
Translation, the process of using genetic code to make proteins, is altered in these cancer cells, resulting in proteins that facilitate growth in the lung environment.
“We found high levels of aspartate in the lungs of mice and patients with breast cancer compared to mice and patients without cancer, which suggests that aspartate may be important for lung metastasis,” first author Ginevra Doglioni, a doctoral student at the Fendt lab, said in a news release,
Aspartate’s presence was surprisingly high in the lungs of mice with metastatic breast cancer, despite its typically low concentrations in blood plasma.
The researchers uncovered that aspartate was not taken up by cancer cells but instead activated a cell surface protein called the NMDA receptor. This activation led to a signaling cascade that ultimately modified a protein known as eIF5A, which kickstarts the translation process. This modification, called ‘hypusination,’ was linked to increased aggressiveness of lung metastases.
Examining human lung tumor samples from patients with metastatic breast cancer, the team found a similar translational program and elevated expression of the NMDA receptor subunit that binds aspartate.
“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. 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,” added Fendt.