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.