Decoded: What triggers spread of cancer cells

Finding and treating cancer at an early stage can save lives. However, treatment becomes more difficult, once the cancer gets metastasised or spreads. Now, a team of researchers in the United States have found how cancer cells are triggered to spread to other parts of the body.

The team at Yale University have also developed a tool which can potentially detect these triggers in patients with renal as well as brain cancers, a finding that could advance treatment.

Metastasis likely occurs through epithelial-mesenchymal transition (EMT) — a process that breaks neighbouring cells apart from each other and sets them in motion, according to the researchers.

Chemical signals or genetic changes in the cells have long been assumed to trigger EMT, but the study showed that a simple change in the texture of the extracellular matrix (ECM), which acts as a scaffold for cells, could be the cause.

A team led by Andre Levchenko, a professor at the Yale Systems Biology Institute, discovered that an alignment of the matrix’s fibres (a common biological occurrence) can trigger the EMT process without or with other stimuli.

“It became clear that in some cancers, before the cells move away from the tumour and spread, there’s a change in the environment,” Levchenko said.

“When these fibres in the matrix align, they create tracks in which the cells move, and we found how it is controlled by complex molecular networks.”

For the study, published in the journal Nature Communications, the team devised a method that mimics the cell environment.

Exploring the EMT process at the molecular level, they discovered two or more molecules inhabiting or activating each other.

While one connected the protein known as YAP to the gene regulator WT1, causing cells to break from each other, the other connected YAP to the protein TRIO. This triggered the cells into motion and even increasing their speed.

This mechanism is particularly active in kidney cancers, the researchers found, but can also control the invasive spread of cells in other cancers, such as glioblastoma.

The discovery can “potentially be used to develop new prognostic tests and pave the way for more personalised clinical interventions,” Levchenko said.

Novel drugs can be developed to target the cells from undergoing the EMT process, he added.

“That would be a very big deal because most of the fatal outcomes we see in cancer are due to metastasis, and therefore, often the EMT process,” Levchenko stated.

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