Scientists have identified a new molecule that allows cancer cells to move freely and spread around the body.

The findings could lead to new treatments capable of preventing the spread of cancer cells around the body through a process called metastasis – the leading cause of death from cancer.

The study, funded by Cancer Research UK and the Institute of Cancer Research (ICR), identified a molecule called YAP as being heavily over-produced in metastatic cancer cells.

YAP is responsible for cells understanding their surrounding environment and can help them move freely if produced in high amounts.

However in normal cells, the pathway is heavily regulated by a number of other molecules produced by neighbouring cells telling each other to stay where they are.

In cancer cells, mutations in genes that produce molecules that interact with the YAP pathway can lead to the pathway permanently being switched on, leading to an over-expression of YAP and the ability for cancer cells to migrate away from their original site.

The mutated gene discovered by the ICR team was beta-PIX – a gene that produces a molecule that encourages the expression of YAP.

The gene was discovered through the systematic switching off of 950 different genes in cancer cells grown in a lab.

Researchers used two sets of cells derived from triple negative breast cancer: one set of cells from the primary tumour – i.e. cells that hadn’t spread – and one set of cells from secondary tumours, i.e. cancer cells that had spread.

The team then switched off beta-PIX signalling in each set of cells to see how it would effect their mobility.

In primary tumour cells, YAP failed to activate once beta-PIX was disabled – an expected result. However in metastatic cells, the same disabling of beta-PIX resulted in YAP being activated, suggesting the cells capable of spreading had disrupted the pathway linking beta-PIX to YAP.

“Cancer cells that have spread around the body have a switch which is jammed on – allowing them to produce a molecule called YAP all the time,” said study leader Dr Chris Bakal, Leader of the Dynamical Cell Systems Team at the ICR. “This allows them to keep growing and spreading throughout the body, ignoring the physical controls that would normally stop this happening.”

“Understanding more about the physical processes which constrain and control the growth and movement of cells can open up exciting new avenues for cancer treatment, which may have been missed until now.”

Dr Emma Smith, science information manager at Cancer Research UK, said: “Understanding more about how cancer spreads could be a crucial first step towards new treatments, but further work is needed to find out if blocking these signals can stop cancer spreading in people.”

Image credit: Institute of Cancer Research

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