“We’re still not targeting the secondary disease enough in the clinic, and I think we need to change this. In our lab, we want to understand: what are the characteristics of cells that are able to metastasise? What are their weaknesses? And how do we target them?Professor Victoria Sanz-Moreno, Queen Mary University of London
17 July 2023
Skin cancer cells rewire their energy systems to spread
Melanoma skin cancer cells rewire their internal power system to drive their spread to other parts of the body, a new study shows.
The research, led by investigators at Barts Cancer Institute and co-authored by researchers from Queen Mary University of London and King’s suggests that reversing this change can make tumour cells less invasive. The team also identified a key molecule that drives this process which could be the key for future therapeutics to halt the spread of cancer.
Cancer cells’ ability to break away from the original tumour and spread to other parts of the body to grow at other sites, called metastasis, causes most cancer deaths. It is currently poorly understood and therefore very difficult to treat.
The study was led by Victoria Sanz-Moreno, Professor of Cancer Cell Biology of Queen Mary University of London, who began the research when she was based at King’s Randall Centre for Cell and Molecular Biophysics.
Melanoma skin cancer is among the quickest-spreading cancer types. If melanoma is diagnosed at an early stage before it spreads, almost all patients in the UK survive their disease for a year or more. But this survival drops to just over half once the disease has spread.
In the new study, published in Nature Communications, the team examined migrating tumour cells. They found that metastasising tumour cells adopt a style of movement where cells maintain a loose connection to their surroundings, enabling them to slither through the tissue. This requires far less energy than the common style of cell movement, where cells grip tightly onto their surroundings and drag themselves through their environment.
They observed that the invasive tumour cells reshape their mitochondria – powerhouses in cells that produce energy for the body - to suit their efficient style of movement adopted during migration. The tumour cells opt to have many, small, fragmented mitochondria that operate in a low-power mode. This contrasts with less-invasive cells, which have large, branching networks of mitochondria that operate in a high-power mode.
The team found that if they manipulate the shape of the mitochondria in their metastasising tumour cells and force them to become more joined up, the cells lose their invasive behaviour. Likewise, if they make mitochondria more disconnected in non-invasive cells, the cells start to behave like metastasising tumour cells. The researchers discovered that a molecule called AMPK sits at the centre of these processes. It senses the energy requirements of the cell and also controls the cytoskeleton, which determines how the cell moves and behaves.
A team from King’s, led by Sasi Conte, Professor of Structural Biology at the Randall Centre, continued to collaborate with Professor Sanz-Moreno’s research group throughout the course of the study. Professor Conte analysed the metabolism of several melanoma cells with different malignancy potential, using the NMR metabolomics Facility.
We are delighted to be able to use our metabolomics expertise in the Core NMR facility to contribute to the understanding of how cancer cells behave and potentially metastasise.”Sasi Conte, Professor of Structural Biology and Head of the Randall Centre
Dr Mark Holt, research fellow at the Randall Centre and School of Cardiovascular and Metabolic Medicine & Sciences, developed bespoke Wolfram Language code to analyse the movement of cancer cells through a 3D collagen matrix.
Patients whose cancer has spread often face tougher treatments and lower chances of survival. These insights about how cancer cells travel around the body could be incredibly valuable for designing interventions to prevent this in the future. The more we know about what’s happening in the bodies of people with cancer, the greater our ability to tackle it will be.”Professor Ketan Patel, Chief Scientist at Cancer Research UK