Research led by Queen Mary University of London, King’s College London and the Francis Crick Institute has identified a protein that makes melanoma, the most serious type of skin cancer, more aggressive by giving cancer cells the ability to change the shape of their nucleus – a characteristic which allows the cells to migrate and spread around the body.
Published in Nature Cell Biology, the study modeled the behavior of aggressive melanoma cells that are able to change the shape of their nucleus to overcome the physical constraints that cancer cells encounter when they migrate through tissues. The study found that these aggressive melanoma cells harbored high levels of a protein called LAP1, and that increased levels of this protein were linked to poor prognosis in melanoma patients.
Melanoma is a type of skin cancer that can spread to other organs in the body. Cancer spread, or metastasis, is the leading cause of cancer-related deaths. While metastasis has been extensively studied, the mechanisms by which it occurs are poorly understood. The findings from the study shed new light on a mechanism of melanoma progression, and could pave the way for the development of new ways to target melanoma spread.
In the study, the team challenged aggressive and less-aggressive melanoma cells in laboratory experiments to migrate through pores in an artificial membrane that were smaller than the size of their nucleus. The aggressive cells were from a site of metastasis in a patient with melanoma, and the less-aggressive cells were from the original or primary melanoma tumor of the same patient.
Imaging conducted after the migration experiments showed that the aggressive cells were able to move through the pores more effectively than the less-aggressive ones by forming bulges at the edge of their nucleus called “blebs.” Genetic analyses of the melanoma cells revealed that the aggressive cells that formed the blebs contained higher levels of the LAP1 protein, which sits within the membrane that surrounds the nucleus (called the nuclear envelope).
Dr. Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said “This new understanding of how the nucleus of a melanoma cell can become more fluid to move around the body is useful for building our knowledge of how cancer works, and opens up a new avenue of investigation into ways to make it harder for cancer to spread.”