Cancer cells can adapt the way they move to spread through different parts of the human body. Now, a team at Cancer Research UK's London Research Institute (LRI; now part of the Francis Crick Institute) has worked out how.
The researchers have uncovered some of the critical machinery that enables the cells to adapt their way of moving to cope with the challenges of moving through different tissues. This is critical for cancer to metastasise - or spread from one organ to another unrelated organ.
The study was led by Drs Erik Sahai, Barry Thompson and Paul Bates at LRI. Dr Sahai explains: "In simple terms, if a cancer cell is to spread from one part of the body to another it will encounter a diverse range of tissue environments. Therefore a successful metastatic cancer cell must be able to move in all these different environments.
"Think of the challenge like an obstacle course. To complete the course you need to move in all sorts of ways (such as running, climbing or crawling) and you need to be able to change how you move depending on the obstacle in front of you. Metastatic cancer cells need similar abilities, just at the microscopic level."
The initial leads for the team's discoveries came from work in fruit flies showing how a small group of cells moves through the fly egg chamber. "I think this provides a stunning example of how ancient methods for cell migration in normal physiology are effectively hijacked by cancer cells. It also highlights how discoveries can come from unexpected angles," said Dr Sahai.
Screening the fruit fly for genes that might be involved in cell migration led the team to focus on components of a large multi-unit protein called STRIPAK. The scientists used a number of molecular biology methods and computer models to study how these components allow breast cancer cells to move in different ways. They found three parts of STRIPAK that play an important role.
These three components are deregulated or mutated in many types of human cancer so the findings are likely to be applicable to other types of cancer too.
The research also showed that the amount of STRIPAK present in a tumour could be linked to breast cancer prognosis. Dr Sahai said: "A significant amount of additional work would be required to determine if this could be turned into a prognostic test that might inform how aggressively the disease should be treated - but this is a possibility."
He also suggests that further work might lead to a new strategy for treatment - but cautions that a lot more research is needed first.
Dr Sahai's team is now looking into what makes cancer cells switch the way they move, speculating that more aggressive cells generally adopt a more favourable way of moving, and that how confined they are in a tissue might play a role.
The paper, STRIPAK components determine mode of cancer cell migration and metastasis, is published in Nature Cell Biology.