GREB1 Is4 is involved in pyrimidine synthesis and causes malignant melanoma, suggesting GREB1 Is4 is a new therapeutic target for melanoma.

GREB1 Isoform4 (Is4) is involved in pyrimidine synthesis and causes malignant melanoma, suggesting GREB1 Is4 a new therapeutic target for melanoma, according to a study in Oncogene.

The expression of a specific isoform of GREB1 Is4  is induced in malignant melanoma cells under the influence of the melanocyte-specific transcription factor (MITF), and GREB1 Is4 promotes cancer cell proliferation and the regulation of pyrimidine metabolism. Furthermore, the anti-tumor effect of antisense nucleic acids against GREB1 showed a potential new modality for malignant melanoma.

To investigate the mechanisms by which GREB1 Is4 is induced in malignant melanoma and involved in its growth, the research group used a mouse model of malignant melanoma and human clinical samples to demonstrate that induction of GREB1 Is4 expression by the MITF transcription factor is important in malignant melanoma development and prognosis.

Subsequent analysis revealed the pathway by which GREB1 activation leads to melanoma cell proliferation. In this study, the research group demonstrated that CAD, the rate-limiting enzyme for pyrimidine synthesis, as a binding protein for GREB1 Is4, and GREB1 Is4 is essential for pyrimidine synthesis in malignant melanoma by biochemical and metabolomic analyses.

GREB1 Is4 has been shown to be a therapeutic target in malignant melanoma, and antisense oligonucleic acids against GREB1 are expected to become new therapeutic agents in the future.