Scientists have discovered a molecular switch that turns on a cancer cell's ability to spread to other parts of the body.
Publishing in this week's Nature, MIT researcher Robert Weinberg and his colleagues were examining microRNAs, small pieces of single-stranded genetic material produced in the cell nucleus. The actions of these RNA sequences are still poorly understood, but they are known to alter the activity of other genes. So, to find out how they might affect the behaviour of certain cancers, the team set out to compare the levels of 29 different microRNAs in tumour cells and healthy tissue. The team also looked at how the levels varied between cancers that had already begun to spread (metastasise), and those that hadn't. Intriguingly, one of the microRNAs - called microRNA-10b - was present at much higher levels in the metastatic tissue, suggesting that it might be involved in triggering the process.
To find out the researchers increased the levels of microRNA-10b in some human breast cancer cells and implanted them into mice. Compared with animals injected with the unmodified cells, animals that received cells containing higher levels of microRNA-10b rapidly developed spreading cancers. Next, to find out how microRNA-10b was triggering this process the team used a computer programme to screen for "targets" - other genes - that might be affected by the microRNA. They were able to home in on a gene called HoxD10, which works like a cellular handbrake, preventing cells from going AWOL. It's switched off by microRNA-10b during embryonic development so that cells can migrate to their correct future locations in the developing body, but in adulthood it is strongly expressed and helps to keep cells stationary.
"During normal development, this microRNA probably enables cells to move from one part of the embryo to another," points out Weinberg. "Its original function has been co-opted by carcinoma [cancer] cells". Excitingly, when the researchers increased the levels of HoxD10 in experimental cancers the cells lost their ability to migrate and invade. This means that it may be possible to exploit the discovery as a powerful anti-cancer target: "I was able to fully reverse microRNA-10b induced migration and invasion, suggesting that HoxD10 is indeed a functional target", says Li Ma, lead author in the study.