by ecancer reporter Audrey Nailor

Cellular plasticity is the ability of living cells to stretch, squirm and squeeze.

Cells use plasticity to defend against infection, migrate to new areas, heal damaged tissue, and take on new roles.

Cancer cells take advantage of plasticity to metastasise, squeezing through tissue and bone to spread to new areas of the body.

Yet the mechanisms behind cell plasticity largely remain a mystery – though new research published in Cell suggests that a key protein may play more roles in cancer than previously thought.

Research conducted at the FIRC Institute of Molecular Oncology and the University of Milan, in collaboration with the Mechanobiology Institute at the National University of Singapore and the Danish Cancer Society Research Centre in Copenhagen, has identified a protein that gives cancer cells the gift of plasticity.

Surprisingly, the culprit appears to be a protein that normally protects against cancer. 

The ATR protein is already known for its crucial role as a damage sensor in DNA repair processes.

After detecting DNA damage, ATR activates p53 – a protein known as 'the guardian of the genome,' because of its key role in preventing the DNA mutations that lead to cancer.

“We have always had the impression that ATR might have functions in the cell under normal conditions, even in the absence of DNA damage,” says Professor Marco Foiani, coordinator of the study.

“We noticed that whenever cells undergo mechanical stress, ATR senses the mechanical vibrations and immediately becomes activated and moves to the nuclear membrane.”

Foiani suspected that ATR played a major role in modulating cellular plasticity, both in response to mechanical stress and during migration.

A battery of laboratory tests confirmed that ATR plays a large role in giving cells their flexibility.

"We pluck the cells with tweezers, we stretch them with suction cups, or we compress them with a piston in the compressive load system to deform them,” says lead author Dr Amit Kumar. 

“This allowed us to [directly] observe the molecular activity of ATR and its crucial role in cellular plasticity.”

ATR's new role may shed clues on the mechanics of stem cell plasticity as well. Some scientists suspect that stem cells may trigger cancer relapses after treatment by acting as reservoirs.

"A cause-and-effect relationship between ATR and stem cell plasticity is highly likely," Foiani says. "We are taking this aspect further by studying ATR in the context of cell differentiation."

Paradoxically, ATR could play dual roles as a tumour suppressor and a driver of tumour metastasis - thus demonstrating a true commitment to flexibility.

Source: FIRC Institute of Molecular Oncology