Ludwig Link

How a neurotransmitter helps initiate melanoma

Richard White, Ludwig Cancer Research Oxford
Richard White

While the BRAF protein is mutated in about half of all melanomas, not all BRAF-mutant melanocytes become malignant. Researchers led by Ludwig Oxford’s Richard White explored whether communication between mutant melanocytes and the surrounding microenvironment determines whether BRAF causes melanoma. Focusing on a type of cell in the microenvironment called a keratinocyte, they used zebrafish and human cells to study this problem. They discovered that the binding of the neurotransmitter GABA secreted by BRAF-mutated melanocytes to the GABA receptor on keratinocytes is essential to the initiation of melanoma and reported in an August paper in Cancer Discovery that this interaction occurs exclusively between keratinocytes and melanocytes that are in direct contact with one another. GABA, which inhibits the electrical activity of neurons, had a similar effect on keratinocytes in culture. It also boosted their secretion of a protein, LIF, that promotes the cancer and increased the growth of those melanocytes. Genetic and pharmacological disruption of GABA production, which was found to be stepped up in melanoma cells, blocked cancer initiation in animal models. The study lends support to the hypothesis of oncogenic competence that Richard has been developing, which proposes that oncogenes can only drive cancers in particular cellular contexts. This work suggests interrupting GABA may be a way to prevent melanoma development in patients.

GABA regulates electrical activity and tumor initiation in melanoma
Cancer Discovery, 2023 August

 Back to November 2023 Ludwig Link

You are now leaving Ludwig Cancer Research's website and are going to a website that is not operated by the association. We are not responsible for the content or availability of linked sites. Do you wish to continue?