Zebrafish study unlocks understanding of developmental mechanisms hijacked in cancer
The work, led by Alessandro Brombin and Liz Patton and in collaboration with Tamir Chandra, could potentially inform improved drug therapies for people living with melanoma: January 2022
Melanoma is the deadliest form of skin cancer and incidence continues to rise in Scotland.
Although current therapies have improved the outcome for many people living with melanoma, sadly, most people with metastatic melanoma still die from the disease. This is in part because the melanoma evolves during progression of the disease with new genetic mutations.
The Patton Lab studies melanoma and the development of the melanocytes – the cells that pigment our hair and skin and the melanoma cells-of-origin – to find novel ways to tackle melanoma.
In a recent study published in Cell Reports, a team of researchers characterised a novel melanocyte stem cell (McSC) population that contribute to adult melanocytes using zebrafish as a model.
They used cutting edge imaging techniques and analysed all the genes expressed (single cell RNA sequencing) during the development of the melanocytes.
The team found that zebrafish McSCs expressed tfap2b – a gene previously found in the McSCs of the hair follicle and importantly identifies a group of therapy-resistant cells in melanoma patients.
Moreover, they validated tfap2b as a functional marker of the McSCs and demonstrated that tfap2b+ McSCs are able to generate all pigment cells in zebrafish and also nerve-associated cells (often present in therapy-resistant melanomas).
This study opens new doors to the understanding of the developmental mechanisms that are hijacked in cancer and paves the way to find novel druggable targets for melanoma.
- Tfap2b specifies an embryonic melanocyte stem cell that retains adult multi-fate potential, published in Cell Reports, 11 January 2022: https://doi.org/10.1016/j.celrep.2021.110234