Exeter College Supernumerary Fellow Richard White authors paper in Nature on melanoma plasticity

Professor Richard White, Supernumerary Fellow at Exeter College and Professor of Genetics, has led a new study out in Nature, titled Mechanical confinement governs phenotypic plasticity in melanoma.

In a collaboration with scientists at Memorial Sloan Kettering Cancer Centre in New York, the paper looks at the ways in which mechanical pressure changes the behaviour of cancer cells. They find that confinement of melanoma cells, a type of skin cancer, causes them to switch to a more invasive and drug-resistant state, a process called phenotypic plasticity. Using a zebrafish model of melanoma alongside analyses of human tumour samples, the researchers show when they are physically restricted by surrounding tissue, they adopt changes in chromatin architecture. This includes activation of a neuronal invasion programme, and the build‑up of a protective “cage” of acetylated tubulin around the nucleus. The DNA‑bending protein HMGB2 plays a central role: under confinement it enhances contact with chromatin, shifts gene expression to invasion, and increases resistance to therapy.

Professor White, whose lab at the Ludwig Institute for Cancer Research (in the Nuffield Department of Medicine) focuses on how environmental and epigenetic cues shape melanoma behaviour, said this finding adds a vital piece to our understanding of how non‑genetic factors drive cancer progression. The work opens potential avenues for interventions aimed at interrupting or reversing the invasive switch in melanoma.

Read the full paper here: Mechanical confinement governs phenotypic plasticity in melanoma.

Concept of a zebrafish grasping and mechanically “squeezing” a tumor.