Shape-shifting cancer cell discovery reveals two potential drug targets against skin cancer

• Cancer cells can change shape to travel around the body and spread
• New technique allows scientists to see cells in 3D, and study how they know where they are and what shape they should change into
• Researchers identified two genes which control how melanoma skin cancer cells change shape in response to their environment – offering two potential drug targets to stop the cancer spreading

Scientists have discovered how skin cancer cells shapeshift based on their environment – enabling them to spread through the body and cause a metastatic cancer.

The discovery of two genes responsible for sensing the environment and adapting cell shape could offer potential new drug targets to stop cancer from metastasising.

Cancer cells can change shape to move around the body, becoming drill-shaped to ‘poke’ through dense tissue like bone, or round and squishy to squeeze through soft tissues and get into the blood.

In a study published in Cell Reports, scientists at The Institute of Cancer Research, London, have uncovered how cells know what environment they are in and therefore which shape to choose.

The team, working in collaboration with researchers at Imperial College London, developed a new system to study cells in 3D – mimicking different parts of the body. Until now, most research has studied cells on hard 2D plastic surfaces.

A unique microscope called stage-scanning oblique plane microscopy (ssOPM) was used to take 3D images of melanoma cells – either stuck to a flat and rigid surface or embedded within a 3D soft collagen hydrogel.

By analysing the 3D images taken of 60,000 cells when certain genes were ‘switched off’, the researchers identified two genes that are important for melanoma cells to change their shape in response to their environment.

The researchers believe these genes, TIAM2 and FARP1, could be targeted to prevent melanoma cancer from metastasising. These genes are good candidates for drug discovery as they have a structure similar to other proteins for which drugs are already in pre-clinical development.

The research team are currently creating AI-based technologies to make predictions about which drugs might be successful, by using these 3D images of cells – which could cut the time taken to develop a drug in half.

This research was funded by The Institute of Cancer Research (ICR) itself, which is both a research institute and a charity, together with Cancer Research UK, Imperial College London, and The Engineering and Physical Sciences Research Council.

Professor Chris Bakal, Professor of Cancer Morphodynamics at The Institute of Cancer Research, London, said:

“Once cancer becomes metastatic and spreads to different parts of the body, it can be quite difficult to treat. For a metastatic cell, travelling across the body is an epic journey where they encounter many different types of landscapes and environments. Up until now, we haven’t known much about how these cells know which environment they are in, in order to change their shape and continue their journey.

“This research has given us insight into the tricks that cancer cells are using to keep growing and spreading. We’ve identified two genes which could, in the future, be targeted to stop melanoma cancer from changing shape and metastasising.”

Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:

“By using an innovative technique to study cells as if they were in a human, rather than in a laboratory, our scientists have uncovered a mechanism which cancer cells are using to move around the body. We know that most cancer deaths occur because cancer has spread from the original tumour to other parts of the body. I hope that further research will lead to the development of new treatments for metastatic melanoma.”

Professor Chris Dunsby, Professor of Biomedical Optics at Imperial College London, said:

“This study is the first to apply a new high-content microscopy technique called oblique plane microscopy to study many thousands of cells in 3D. In the future, we hope that the approach demonstrated here can be applied to address a wide range of questions in cancer biology.”

The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations. Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

The ICR is a charity and relies on support from partner organisations, funders and the general public. A member institution of the University of London, it is one of the UK’s leading higher education institutions, placing first for biological sciences and second overall in the definitive ‘REF2021’ rankings of UK university research quality, impact and environment, and provides postgraduate higher education of international distinction.

The ICR's mission is to make the discoveries that defeat cancer.

For more information visit ICR.ac.uk