文章：

CUX1，一种单倍不足的肿瘤抑制基因，在晚期癌症中过度表达

CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers

原文发布日期：2014-09-05

DOI: 10.1038/nrc3805

类型: Review Article

开放获取: 否

要点：

1. CUT-like homeobox 1 (CUX1) undergoes loss-of-heterozygosity (LOH) and loss-of-function somatic point mutations in several cancers. As no mutations are found in the remaining allele, CUX1 seems to be a haploinsufficient tumour suppressor gene.
2. Copy number gains are much more frequent than losses in cancers arising from many different types of tissue, including cancers that have a high frequency of loss-of-function mutations. Increased CUX1 copy number and expression levels are associated with shorter disease-free survival.
3. The accumulated evidence suggests that decreased CUX1 expression facilitates tumour initiation, whereas increased CUX1 expression promotes tumorigenic progression.
4. One CUX1 protein isoform functions as an ancillary factor in base excision repair. Other CUX1 isoforms function as transcriptional repressors or activators, depending on promoter context.
5. Cellular functions of CUX1 that promote tumour development involve cell cycle progression, cell migration and invasion, resistance to apoptosis, promotion of bipolar mitosis in the presence of multiple centrosomes, accelerated repair of oxidative DNA damage and modulation of the tumour microenvironment.
6. Cellular functions of CUX1 that suppress tumour development include inhibition of the PI3K–AKT pathway and a direct role in base excision repair.

要点翻译：

1. CUX1同源框1（CUX1）在多种癌症中经历杂合性缺失（LOH）和功能丧失性体细胞点突变。由于在剩余等位基因中未发现突变，CUX1似乎是一种单倍体不足的肿瘤抑制基因。
2. 在多种组织来源的癌症中（包括高频发生功能丧失突变的癌症），拷贝数增加远比缺失更为常见。CUX1拷贝数及表达水平的升高与较短的无病生存期相关。
3. 现有证据表明：CUX1表达下调促进肿瘤发生，而CUX1表达上调则驱动肿瘤进展。
4. 一种CUX1蛋白亚型在碱基切除修复中起辅助因子作用。其他CUX1亚型则根据启动子环境差异，发挥转录抑制因子或激活因子的功能。
5. CUX1促进肿瘤发展的细胞功能包括：调控细胞周期进程、细胞迁移与侵袭、抗凋亡、在多中心体存在条件下促进双极有丝分裂、加速氧化性DNA损伤修复以及调节肿瘤微环境。
6. CUX1抑制肿瘤发展的细胞功能则包括：抑制PI3K–AKT通路以及在碱基切除修复中发挥直接作用。

英文摘要：

CUT-like homeobox 1 (CUX1) is a homeobox gene that is implicated in both tumour suppression and progression. The accumulated evidence supports a model of haploinsufficiency whereby reduced CUX1 expression promotes tumour development. Paradoxically, increased CUX1 expression is associated with tumour progression, and ectopic CUX1 expression in transgenic mice increases tumour burden in several tissues. One CUX1 isoform functions as an ancillary factor in base excision repair and the other CUX1 isoforms act as transcriptional activators or repressors. Several transcriptional targets and cellular functions of CUX1 affect tumorigenesis; however, we have yet to develop a mechanistic framework to reconcile the opposite roles of CUX1 in cancer protection and progression.

摘要翻译： 

CUT样同源框1（CUX1）是一个同源框基因，兼具肿瘤抑制与促进肿瘤进展的双重作用。现有证据支持一种单倍剂量不足的模型：CUX1表达降低会促进肿瘤发生。然而矛盾的是，CUX1表达升高又与肿瘤进展相关，且在转基因小鼠中异位表达CUX1会增加多种组织的肿瘤负荷。CUX1的一种异构体可作为碱基切除修复的辅助因子，其它异构体则发挥转录激活或抑制作用。CUX1的若干转录靶标及细胞功能均影响肿瘤发生；然而，我们尚未建立能够统一解释CUX1在癌症保护与进展中相反作用的机制框架。

原文链接：

CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers