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仅含同源盒结构域的蛋白同源盒(HOPX)与结直肠癌

The homeobox only protein homeobox (HOPX) and colorectal cancer.

作者信息

Yamashita Keishi, Katoh Hiroshi, Watanabe Masahiko

机构信息

Department of Surgery, Kitasato University School of Medicine, Asamizodai 2-1-1, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.

出版信息

Int J Mol Sci. 2013 Nov 25;14(12):23231-43. doi: 10.3390/ijms141223231.

Abstract

The HOP (homeobox only protein) homeobox (HOPX) is most closely related to the homeobox protein that contains a homeobox-like domain but lacks certain conserved residues required for DNA binding. Here, we review the current understanding of HOPX in the progression of colorectal cancer (CRC). HOPX was initially reported as a differentiation marker and is expressed in various normal tissues. In the colon, HOPX is expressed uniquely in the quiescent stem cell, +4, and in differentiated mucosal cells of the colon. HOPX expression is markedly suppressed in a subset of cancers, mainly in an epigenetic manner. CRC may include separate entities which are differentially characterized by HOPX expression from a prognostic point of view. HOPX itself can regulate epigenetics, and defective expression of HOPX can result in loss of tumor suppressive function and differentiation phenotype. These findings indicate that HOPX may be both a central regulator of epigenetic dynamics and a critical determinant for differentiation in human cells. HOPX downstream targets were identified in CRC cell lines and hold promise as candidates for therapeutic targets of CRC, such as EphA2 or AP-1. Further analysis will elucidate and confirm the precise role of such proteins in CRC progression.

摘要

仅含同源框蛋白(HOP)同源框(HOPX)与含类同源框结构域但缺乏DNA结合所需某些保守残基的同源框蛋白关系最为密切。在此,我们综述了目前对HOPX在结直肠癌(CRC)进展中的认识。HOPX最初被报道为一种分化标志物,在多种正常组织中表达。在结肠中,HOPX仅在静止干细胞(+4)和结肠分化黏膜细胞中表达。HOPX表达在一部分癌症中显著受到抑制,主要是通过表观遗传方式。从预后角度来看,CRC可能包括以HOPX表达差异为特征的不同实体。HOPX本身可调节表观遗传学,HOPX表达缺陷可导致肿瘤抑制功能和分化表型丧失。这些发现表明,HOPX可能既是表观遗传动力学的核心调节因子,也是人类细胞分化的关键决定因素。在CRC细胞系中鉴定出了HOPX下游靶点,有望成为CRC治疗靶点的候选物,如EphA2或AP - 1。进一步分析将阐明并确认这些蛋白在CRC进展中的确切作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d11/3876040/80bebd5c21f6/ijms-14-23231f1.jpg

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