SATB (Special AT-rich binding protein) family proteins have emerged as key regulators that integrate higher-order chromatin organization with the regulation of gene expression. Studies over the past decade have elucidated the specific roles of SATB1 and SATB2, two closely related members of this family, in cancer progression. SATB family chromatin organizers play diverse and important roles in regulating the dynamic equilibrium of apoptosis, cell invasion, metastasis, proliferation, angiogenesis, and immune modulation. This review highlights cellular and molecular events governed by SATB1 influencing the structural organization of chromatin and interacting with several co-activators and co-repressors of transcription towards tumor progression. SATB1 expression across tumor cell types generates cellular and molecular heterogeneity culminating in tumor relapse and metastasis. SATB1 exhibits dynamic expression within intratumoral cell types regulated by the tumor microenvironment, which culminates towards tumor progression. Recent studies suggested that cell-specific expression of SATB1 across tumor recruited dendritic cells (DC), cytotoxic T lymphocytes (CTL), T regulatory cells (Tregs) and tumor epithelial cells along with tumor microenvironment act as primary determinants of tumor progression and tumor inflammation. In contrast, SATB2 is differentially expressed in an array of cancer types and is involved in tumorigenesis. Survival analysis for patients across an array of cancer types correlated with expression of SATB family chromatin organizers suggested tissue-specific expression of SATB1 and SATB2 contributing to disease prognosis. In this context, it is pertinent to understand molecular players, cellular pathways, genetic and epigenetic mechanisms governed by cell types within tumors regulated by SATB proteins. We propose that patient survival analysis based on the expression profile of SATB chromatin organizers would facilitate their unequivocal establishment as prognostic markers and therapeutic targets for cancer therapy.

中文翻译：

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SATB家族的染色质组织者是肿瘤进展的主要调节者。

SATB（富含特殊AT的结合蛋白）家族蛋白已成为关键调节剂，将高级染色质组织与基因表达调节相结合。过去十年的研究阐明了该家族中两个密切相关的成员SATB1和SATB2在癌症进展中的具体作用。SATB家族的染色质组织者在调节细胞凋亡，细胞侵袭，转移，增殖，血管生成和免疫调节的动态平衡中起着多种重要作用。这篇综述重点介绍了由SATB1控制的细胞和分子事件，这些事件影响染色质的结构组织并与转录的几种共激活因子和共抑制因子相互作用，从而促进肿瘤的发展。跨肿瘤细胞类型的SATB1表达产生细胞和分子异质性，最终导致肿瘤复发和转移。SATB1在受肿瘤微环境调节的肿瘤内细胞类型中表现出动态表达，最终达到肿瘤进展。最近的研究表明SATB1在肿瘤募集的树突状细胞（DC），细胞毒性T淋巴细胞（CTL），T调节细胞（Tregs）和肿瘤上皮细胞以及肿瘤微环境中的细胞特异性表达是肿瘤进展和肿瘤炎症的主要决定因素。相反，SATB2在多种癌症类型中差异表达，并参与肿瘤发生。对与SATB家族染色质组织者表达相关的多种癌症类型患者的生存分析表明，SATB1和SATB2的组织特异性表达有助于疾病的预后。在这种情况下，有必要了解由SATB蛋白质调控的肿瘤中由细胞类型决定的分子参与者，细胞途径，遗传和表观遗传机制。我们建议基于SATB染色质组织者的表达谱的患者生存分析将有助于他们明确地确立为癌症治疗的预后标志物和治疗靶标。