Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia 20037, USA.
Cancer Res. 2012 Jan 15;72(2):387-94. doi: 10.1158/0008-5472.CAN-11-2345.
Cancer cells frequently exhibit deregulation of coregulatory molecules to drive the process of growth and metastasis. One such group of ubiquitously expressed coregulators is the metastasis-associated protein (MTA) family, a critical component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA1 occupies a special place in cancer biology because of its dual corepressor or coactivator nature and widespread overexpression in human cancers. Here, we highlight recent advances in our understanding of the vital roles of MTA1 on transformation, epithelial-mesenchymal transition, and the functions of key cancer-relevant molecules such as a nexus of multiple oncogenes and tumor suppressors. In addition to its paramount role in oncogenesis, we reveal several new physiologic functions of MTA1 related to DNA damage, inflammatory responses, and infection, in which MTA1 functions as a permissive "gate keeper" for cancer-causing parasites. Further, these discoveries unraveled the versatile multidimensional modes of action of MTA1, which are independent of the NuRD complex and/or transcription. Given the emerging roles of MTA1 in DNA repair, inflammation, and parasitism, we discuss the possibility of MTA1-targeted therapy for use not only in combating cancer but also in other inflammation and pathogen-driven pathologic conditions.
癌细胞经常表现出调节核心调控分子的失调，以推动生长和转移的过程。其中一组广泛表达的核心调节剂是转移相关蛋白（MTA）家族，它是核小体重塑和组蛋白去乙酰化酶（NuRD）复合物的关键组成部分。由于 MTA1 具有双重核心抑制子或共激活子性质以及在人类癌症中的广泛过表达，因此在癌症生物学中占有特殊地位。在这里，我们强调了最近对 MTA1 在转化、上皮-间充质转化以及关键癌症相关分子功能方面的重要作用的理解的最新进展，如多个癌基因和肿瘤抑制因子的枢纽。除了在肿瘤发生中的重要作用外，我们还揭示了与 DNA 损伤、炎症反应和感染相关的 MTA1 的几个新的生理功能，其中 MTA1 作为致癌寄生虫的允许“守门员”发挥作用。此外，这些发现揭示了 MTA1 的多功能多维作用模式，这些模式独立于 NuRD 复合物和/或转录。鉴于 MTA1 在 DNA 修复、炎症和寄生虫感染中的新兴作用，我们讨论了针对 MTA1 的靶向治疗的可能性，不仅用于对抗癌症，还用于其他炎症和病原体驱动的病理状况。
