The researchers used a robotic microscope to record the formation of drills from melanoma cells grown on a three-dimensional skin-like material in the lab. The drills help cancer cells attach to and make holes in surrounding cells and structures, allowing the cancer to move beyond where it forms and reach other tissues and organs. “This is the first time this type of cell shape change has been associated with any type of metastatic cancer,” said Chris Bakal, professor of cancer morphodynamics at the Institute of Cancer Research in London. Melanoma rates have more than doubled in the UK since the 1990s, with more than 16,000 people newly diagnosed with the disease each year. In the early stages, tumors can often be removed by surgeons, but the cancer becomes more difficult to treat as it spreads to other parts of the body. Bakal and his colleagues grew melanoma cells in a three-dimensional matrix rich in collagen, one of the main proteins found in the skin. By knocking out the genes in the cancer cells one by one, they discovered a particular gene, ARHGEF9, which was crucial for the formation of the molecular drills. The gene is found in all human cells, but in adults it tends to be activated only in brain cells to help them make new connections. Much earlier in human development, the gene allows neurons to produce their own drill-like structures, which help cells spread through the body and wire the nervous system. Writing in the journal iScience, the researchers describe how turning off the ARHGEF9 gene in melanoma cells destabilized the molecular drills so the cancer could no longer attach to and drill into neighboring tissues. The finding raises hopes for new treatments for melanoma and possibly other cancers, such as neuroblastoma, that can spread in the same way. Although mutations in the ARHGEF9 gene are associated with a wide range of neurological disorders, the gene is thought to be more important during early development than in adulthood. If this is the case, the development of drugs to inhibit the gene may prevent melanoma from spreading without serious side effects. “We think disarming the drill is likely to have broad application,” Bakal said, though he suspects the procedure won’t be relevant for all melanomas. Because the gene is very active in metastatic cells and less so in many other normal cells, drugs that target it may be more selective in cancer cells and less toxic, he added. Subscribe to First Edition, our free daily newsletter – every morning at 7am. BST Beyond paving the way for future treatments, the work may have much broader implications for understanding cancer. “This work could ultimately change the way we think about cancer cells and tumors. Specifically, neurons interact in large networks to form brains, talk through neurotransmitters, and spread information through electricity,” Bakal said. “Our work shows that many cancer cells can act similarly to form these networks and that tumors can be almost ‘brain-like’. The exercises or sensors we identified here could be a way that cancer cells connect to this network and pass information to each other.” Further work in the laboratory suggests that cancer cells are electrically very active. Dr Sam Godfrey at Cancer Research UK said the results were encouraging. “These findings will allow future research to focus on the role of this target in melanoma and whether it could also help us defeat some cancers that affect children and young people,” he said. “Understanding more about the biology of this disease will lead to new tests and treatments for people with melanoma.”
