Blevins Melanie A, Huang Mingxia, Zhao Rui
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado.
Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado.
Mol Cancer Ther. 2017 Jun;16(6):981-990. doi: 10.1158/1535-7163.MCT-16-0592.
Transcriptional corepressor proteins have emerged as an important facet of cancer etiology. These corepressor proteins are often altered by loss- or gain-of-function mutations, leading to transcriptional imbalance. Thus, research directed at expanding our current understanding of transcriptional corepressors could impact the future development of new cancer diagnostics, prognostics, and therapies. In this review, our current understanding of the CtBP corepressors, and their role in both development and disease, is discussed in detail. Importantly, the role of CtBP1 overexpression in adult tissues in promoting the progression of multiple cancer types through their ability to modulate the transcription of developmental genes ectopically is explored. CtBP1 overexpression is known to be protumorigenic and affects the regulation of gene networks associated with "cancer hallmarks" and malignant behavior, including increased cell survival, proliferation, migration, invasion, and the epithelial-mesenchymal transition. As a transcriptional regulator of broad developmental processes capable of promoting malignant growth in adult tissues, therapeutically targeting the CtBP1 corepressor has the potential to be an effective method for the treatment of diverse tumor types. Although efforts to develop CtBP1 inhibitors are still in the early stages, the current progress and the future perspectives of therapeutically targeting this transcriptional corepressor are also discussed. .
转录共抑制蛋白已成为癌症病因学的一个重要方面。这些共抑制蛋白常常因功能丧失或功能获得性突变而发生改变,导致转录失衡。因此,旨在拓展我们目前对转录共抑制蛋白理解的研究可能会影响新型癌症诊断、预后评估和治疗方法的未来发展。在这篇综述中,我们将详细讨论目前对CtBP共抑制蛋白的理解,以及它们在发育和疾病中的作用。重要的是,探讨了成年组织中CtBP1过表达通过其异位调节发育基因转录的能力促进多种癌症类型进展的作用。已知CtBP1过表达具有促肿瘤作用,并影响与“癌症特征”和恶性行为相关的基因网络调控,包括增加细胞存活、增殖、迁移、侵袭以及上皮-间质转化。作为一种能够促进成年组织恶性生长的广泛发育过程的转录调节因子,靶向CtBP1共抑制蛋白进行治疗有可能成为治疗多种肿瘤类型的有效方法。尽管开发CtBP1抑制剂的努力仍处于早期阶段,但也将讨论靶向这种转录共抑制蛋白进行治疗的当前进展和未来前景。