New research shows how cancer cells break free of physical restraints to grow and spread


New research carried out by scientists at The Institute of Cancer Research (ICR) in London has shown how cancer cells can break free of the physical restraints imposed by their surroundings to grow and spread around the body.

Funded by Cancer Research UK and ICR, the new study has found these cancer cells have a broken switch that continually activates a key molecule YAP that acts as a ‘mechano-sensor’.

Due to this, cells can ‘feel’ the matrix around them and can grasp onto it to move around tissues in the body.

ICR dynamical cell systems team study leader Dr Chris Bakal said: “Our research shows how cancer cells that have become invasive are able overcome the normal constraints on cell movement.

“Cancer cells that have spread around the body have a switch that is jammed on, allowing them to produce a molecule called YAP all the time.

“This allows them to keep growing and spreading throughout the body, ignoring the physical controls that would normally stop this happening.”

YAP can help to overcome the physical restraints such as suppression of cell movement by contact with other cells by turning on various genes that are usually switched off.

The molecule’s activity is carefully regulated in most cells, but the researchers found that cancer cells that spread are able to produce YAP all the time.

In order to work out the ones that influenced YAP signalling, the ICR team systematically switched off 950 different genes in cancer cell lines that are grown in the laboratory.

The team found that it was partially controlled by a molecule called beta-PIX, which boosts YAP activity as the cell binds to the extracellular matrix while moving through tissue.

When the cells were forced to remain stuck to the matrix, YAP activity was even higher, but the activity was reduced when beta-PIX molecules were depleted.

The team looked at triple-negative breast cancer cells in the lab in order to find out how YAP activity was controlled in cancer cells.

"Our research shows how cancer cells that have become invasive are able overcome the normal constraints on cell movement."

These cancer cells were either derived from a primary tumour or from a site of distant spread.

YAP could not activate when the beta-PIX pathway was disabled in cancer cells from the primary tumour.

But when the same was done to the metastatic cells, YAP did activate.

This reveals that invasive cancer cells have broken the pathway that links beta-PIX to YAP and allow them to sustain high levels of YAP.


Image: An image showing 384 experiments from the study, including around 20,000 single cells. Photo: courtesy of The Institute of Cancer Research.