A team of experts recently discovered that the availability of the amino acid aspartate is one of the reasons why the lung is a frequent organ of metastasis.
More than half of patients with cancer that has spread beyond the primary site have lung metastasesbut scientists were unaware of what makes this organ such a tempting place for cancer cells.
To solve the mystery, researcher Sarah-Maria Fendt and her team at the VIB-KU Leuven Center for Cancer Biology investigated gene expression in cells from aggressive lung metastases and found a alternative “translation program”.
Translation is the process that uses genetic code as a template to produce proteins in cells. A change in the translational program results in a set of different proteins that allow cancer cells to grow more easily in the lung environment.
What kicks off this alternative translational program in aggressive metastases is a amino acid. “We found high levels of aspartate in the lungs of animal guinea pigs and patients with breast cancer compared to guinea pigs and patients without the disease, which suggests that aspartate may be important for lung metastasis”, explained researcher Ginevra Doglioni, cited by .
Aspartate is an amino acid with very low concentrations in blood plasma, but, surprisingly, very high concentrations in the lungs of mice with metastatic breast cancer.
There are several proteins with the potential to affect the translation process, namely the so-called initiation factors. One of these initiation factors is the eIF5Awhich starts the translation.
In cancer cells within lung metastases, scientists found an activating modification of eIF5A called hypusinationwhich was associated with greater aggressiveness of cancer from lung metastases.
Aspartate was responsible for triggering this modification in eIF5A through an unexpected mechanism. Surprisingly, the amino acid was not absorbed by the cancer cells, but instead activated a cell surface protein called the NMDA receptor in cancer cells, causing a true signaling cascade that eventually triggered the hypsination of eIF5A.
This phenomenon drives the translational program that increases the ability of cancer cells to change their environment and make it more suitable for aggressive growth.
The findings were published on the first day of the year, in Nature.
