In a study recently published in the "British Journal of Cancer", a research team led by Mario Mikula from MedUni Vienna has shown that human skin organoids can be used to study the growth of malignant melanoma. The investigations using this instrument, which is extremely valuable for basic research, revealed that the loss of the neuronal protein NLGN4X in melanoma is associated with the progression of the disease, and that the loss of the neuronal protein NLGN4X is associated with the progression of the disease.
"The generation of human skin from a single embryonic stem cell has been known since 2020. We have now succeeded in using this model for melanoma research," reports Mario Mikula from the Center for Pathobiochemistry and Genetics at the Medical University of Vienna. "Organoid research has made it possible to better simulate the disease progression of patients in the laboratory. In future, we will also use liver and intestinal organoids in the TOPICO cooperation project funded by the Austrian Science Fund (FWF) to test new treatment options," says Mikula.
Important mechanism in melanoma clarified
While NLGN4X is highly expressed in mature melanocytes, the studies have shown that reduced NLGN4X expression is associated with melanoma progression in patient cohorts. By restoring NLGN4X expression in late-stage melanoma lines, we observed reduced tumour growth after transplantation into human skin organoids. Mechanistically, this project showed that suppression of NLGN4X downregulates the VBP1 protein. The loss of VBP1 leads to the accumulation of HIF1A, which in turn is important for the migration properties of melanoma. These results show that the reduction of NLGN4X represents a new mechanism for HIF induction. The research results could improve the prognosis for affected patients and point to new ways of treating metastatic melanoma.
Publication: British Journal of Cancer
Late stage melanoma is hallmarked by low NLGN4X expression leading to HIF1A accumulation;
David Schörghofer, Laurenz Vock, Madalina A. Mirea, Oliver Eckel, Anna Gschwendtner, Jürgen Neesen, Erika Richtig, Markus Hengstschläger & Mario Mikula
Doi: 10.1038/s41416’024 -02758-9
’024 -02758-9
