Mesothelioma is a rare and fatal form of cancer that forms in the thin lining around the lungs. Though thousands die from the disease every year, doctors and scientists still have little understanding of how it progresses, and that has worked against finding effective ways to treat it. Recently, a team of scientists from The First and Second Affiliated Hospital of Xi’an Jiaotong University reported having found a protein that seems to help this cancer grow and spread. Their study, published in the journal Molecular Biology Reports, may present a new target for treatment.
Mesothelioma Cells and a Helper Protein Called USP14
Like all cells in the body, mesothelioma cells are filled with proteins that do different jobs, including marking old or unneeded proteins with tiny tags called ubiquitin that signal when they are no longer needed. One protein, called USP14, works against this process, essentially removing those tags so that the proteins it touches stay around longer. The researchers found that mesothelioma cells contain high levels of USP14 and set out to determine its role.
The scientists reported that mesothelioma cells behaved very differently when they disabled USP14. In mice with mesothelioma tumors, switching off USP14 slowed the tumors’ growth. The aggressive cancer cells grew more slowly and formed fewer new colonies. The elimination of the protein’s activity also limited the cells’ motility and ability to spread into nearby areas, and many of the cells died. Conversely, mesothelioma cells without USP14 also showed more autophagy, which is how a cell breaks down and recycles its own worn-out components. USP14 seems to depress this process.
Mesothelioma and a Chain of “Grow” Signals
Mesothelioma cells rely on a protein called YAP1 to survive, and the research showed that USP14 attaches itself to YAP1 and deactivates the signals that would lead to its destruction. This allows YAP1and another protein, TEAD4, to continue sending “grow” signals to the deadly cell. The scientists also found that mesothelioma cells that lost USP14 became aggressive again when they were combined with YAP1 or TEAD4. This demonstrates that the three proteins work together.
Though this study’s results were derived from lab animals, they give mesothelioma researchers a new target. A drug that could block USP14 might help slow the aggressive form of asbestos-related cancer’s growth, offering longer survival and better quality of life.
If you or someone you love has been diagnosed with mesothelioma, the Patient Advocates at Mesothelioma.net can connect you with valuable resources. Contact us today at 1-800-692-8608 to learn more.