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特异性富含 AT 的序列结合蛋白 1(SATB1)及其在实体瘤中的作用。

The Special AT-rich Sequence Binding Protein 1 (SATB1) and its role in solid tumors.

机构信息

Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Faculty of Medicine, Leipzig University, Leipzig, Germany.

Molecular Oncology, Faculty of Medicine, Leipzig University, Leipzig, Germany.

出版信息

Cancer Lett. 2018 Mar 28;417:96-111. doi: 10.1016/j.canlet.2017.12.031. Epub 2018 Jan 4.

Abstract

The Special AT-rich Sequence Binding Protein 1 (SATB1) exerts multiple functions, by influencing the structural organization of chromatin and interacting with several co-activators and co-repressors of transcription. Thus, SATB1 affects the expression of various genes by multiple mechanisms of action, involving three-dimensional chromatin architecture. More recently, SATB1 has been connected with solid tumors, tumorigenesis, tumor progression and tumor immunity. On the diagnostic side, SATB1 levels were found to correlate with clinicopathological features like increased TNM stage, reduced tumor differentiation, and a shorter overall survival. SATB1 expression was also identified as an independent prognostic marker in various cancers. Moreover, different gene knockdown or ectopic overexpression strategies in cancer cells have identified SATB1 to affect proliferation, cell cycle, apoptosis, cell morphology / cell polarity, EMT and multidrug-resistance as well as tumor formation, growth, invasion and metastasis in vivo. These processes are mediated through a great multitude of SATB1 target genes, including many (proto-) oncogenes. Functional and molecular studies on SATB1 in various cancers are comprehensively summarized, and the prospects and caveats of SATB1 as tumor marker and as putative target molecule are discussed.

摘要

特殊富含 AT 的序列结合蛋白 1(SATB1)通过影响染色质的结构组织,并与转录的几个共激活因子和共抑制因子相互作用,发挥多种功能。因此,SATB1 通过涉及三维染色质结构的多种作用机制影响各种基因的表达。最近,SATB1 与实体瘤、肿瘤发生、肿瘤进展和肿瘤免疫有关。在诊断方面,SATB1 水平与临床病理特征相关,如 TNM 分期增加、肿瘤分化降低以及总生存期缩短。SATB1 表达也被确定为各种癌症的独立预后标志物。此外,在癌细胞中使用不同的基因敲低或异位过表达策略,已经确定 SATB1 可以影响增殖、细胞周期、细胞凋亡、细胞形态/细胞极性、EMT 和多药耐药性,以及体内的肿瘤形成、生长、侵袭和转移。这些过程是通过大量的 SATB1 靶基因介导的,包括许多(原)癌基因。本文全面总结了 SATB1 在各种癌症中的功能和分子研究,并讨论了 SATB1 作为肿瘤标志物和潜在靶分子的前景和注意事项。

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