Histone code reader SPIN1 is a promising target of cancer therapy.

SPIN1 is a histone methylation reader, which can epigenetically control multiple tumorigenesis-associated signaling pathways, including the Wnt, PI3K/AKT, and RET pathways. Considerable evidence has shown that SPIN1 is overexpressed in many cancers, which can promote cell proliferation, transformation, metastasis, and chemical or radiation resistance. With the growing understanding of the SPIN1 protein structure, some inhibitors have been developed to interfere with the recognition between SPIN1 and histone H3K4me3 and H3R8me2a methylation and block the oncogenic functions of SPIN1. Therefore, SPIN1 is a potential target of cancer therapy. However, the mechanism by which SPIN1-transformed cells overcome the significant mitotic spindle defects and the factors promoting SPIN1 overexpression in cancers remain unclear. In this review, we described the current understanding of the SPIN1 protein structure and its expression, functions, and regulatory mechanisms in carcinogenesis, and discussed the challenges faced in the mechanisms of SPIN1 overexpression and oncogenic functions, and the potential application of anti-SPIN1 treatment in human cancers.