A family of proteins known as 'ROCK' regulate the shape and movement of cells, and in doing so help to control tumour growth, a new study reveals.
Scientists found that loss of either the Rock1 or Rock2 genes had no effect on tumour growth, but that deleting both genes prevented tumours from forming.
The research, published in the journal eLIFE, highlights the possibility that inhibiting the ROCK proteins could be an effective new strategy for treating cancer.
The study was led by the late Professor Chris Marshall at The Institute of Cancer Research, London, in collaboration with the Cancer Research UK Manchester Institute. It was funded by Cancer Research UK.
ROCK proteins are known to control key aspects of the invasion of cancer cells into new tissue, but their role in cell proliferation, and in the initiation or progression of cancer, has been unclear.
To investigate this, researchers used two types of mice with either lung cancer – one of the most common and lethal types of cancer – or melanoma – the most deadly form of skin cancer. They also tested cells isolated from these mice.
Deleting both the Rock1 and Rock2 genes prevented tumour growth in both mouse models, but loss of just one of the genes did not stop tumours growing. Similar results were seen in cell lines taken from mice.
'Potential cancer treatment'
Researchers found that loss of the Rock genes triggers a drop in cell cycle proteins, causing cells to enter a state of suspended animation. The downregulation of these proteins seemed to occur because of a malfunction in the signalling that controls cell movement and shape, caused by the loss of ROCK.
Interestingly, deletion of the Rock1 gene in the mice with lung cancer appeared to increase tumour mass, while in mice with melanoma, deleting Rock2 led to acceleration in tumour formation.
One of the authors of the study Dr Faraz Mardakheh, a Postdoctoral Training Fellow in the Division of Cancer Biology at the ICR, said: “Our results show that ROCK proteins play a key role not only in the movement and spread of cancer cells, but also in the growth of tumours.
“The research highlights the need to explore ROCK inhibitors as potential cancer treatment. But how ROCK inhibitors are designed will be critical, as it’s clear that incomplete inhibition of ROCK, or specific inhibition of only one form, might not be effective.”