The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Endodontics, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Biochimie. 2021 Dec;191:78-86. doi: 10.1016/j.biochi.2021.09.002. Epub 2021 Sep 4.
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.
SPIN1 是一种组蛋白甲基化读码器，可通过表观遗传控制多种与肿瘤发生相关的信号通路，包括 Wnt、PI3K/AKT 和 RET 通路。大量证据表明，SPIN1 在许多癌症中过表达，可促进细胞增殖、转化、转移以及化学或辐射耐药性。随着对 SPIN1 蛋白结构的认识不断加深，已经开发出一些抑制剂来干扰 SPIN1 与组蛋白 H3K4me3 和 H3R8me2a 甲基化的识别，从而阻断 SPIN1 的致癌功能。因此，SPIN1 是癌症治疗的潜在靶点。然而，SPIN1 转化细胞如何克服明显的有丝分裂纺锤体缺陷以及促进癌症中 SPIN1 过表达的因素尚不清楚。在本文中，我们描述了对 SPIN1 蛋白结构及其在致癌作用中的表达、功能和调控机制的最新认识，并讨论了 SPIN1 过表达和致癌功能机制中面临的挑战，以及抗 SPIN1 治疗在人类癌症中的潜在应用。
