KMT2C, also known as MLL3, is a histone lysine methyltransferase responsible for the monomethylation of histone 3 lysine 4 (H3K4) residues at gene enhancer sites. It is part of the KMT2C/D COMPASS complexes, which regulate DNA promoter and enhancer elements, modulating gene expression in various cell types crucial for embryonic development, central nervous system development, and post-natal survival [3]. It is involved in multiple signaling pathways such as EMT, p53, Myc, and DNA damage repair [5].

In SCLC mouse models, KMT2C deficiency promoted multiple-organ metastases. Mechanistically, KMT2C regulated DNMT3A expression through histone methylation, and forced DNMT3A expression restrained metastasis [1]. In non-metastatic murine models of TNBC, deletion of Kmt2c drove metastasis, especially to the brain, via KDM6A-dependent upregulation of MMP3 [2]. KMT2C knockout in cortical neurons and the mouse brain led to ASD-like behaviors [4]. In a Pten-deficient PCa mouse model, deletion of the Kmt2c SET domain drove proliferation, PIN formation, and metastatic dissemination [6].

In conclusion, KMT2C plays a crucial role in various biological processes through its histone methylation function. Gene knockout mouse models have revealed its significance in cancer metastasis, such as in SCLC, TNBC, and prostate cancer, as well as in neurodevelopmental disorders like ASD. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.