The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target.
The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target.
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DOI：
10.1158/1535-7163.mct-16-0592
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发表时间：
2017-06
影响因子：
5.7
通讯作者：
Zhao R
中科院分区：
文献类型：
--
作者：
Blevins MA;Huang M;Zhao R
转录辅阻遏蛋白已成为癌症病因学的重要方面。这些辅阻遏蛋白通常被功能丧失或获得突变改变，导致转录失衡。因此，旨在扩大我们目前对转录辅助抑制因子的理解的研究可能会影响新的癌症诊断，诊断和治疗的未来发展。在这篇综述中，我们目前的理解CtBP的辅抑制因子，以及它们在发展和疾病中的作用，进行了详细讨论。重要的是，CtBP 1过表达在成人组织中的作用，促进多种癌症类型的发展，通过他们的能力，异位调节发育基因的转录进行了探讨。已知CtBP 1过表达是促肿瘤发生的，并影响与“癌症标志”和恶性行为相关的基因网络的调节，包括：增加的细胞存活、增殖、迁移、侵袭和上皮-间质转化（EMT）。作为能够促进成人组织中恶性生长的广泛发育过程的转录调节因子，治疗靶向CtBP 1共阻遏物具有成为治疗不同肿瘤类型的有效方法的潜力。虽然开发CtBP 1抑制剂的努力仍处于早期阶段，但也讨论了目前的进展和未来的治疗前景。
Transcriptional co-repressor proteins have emerged as an important facet of cancer etiology. These co-repressor proteins are often altered by loss- or gain-of-function mutations, leading to transcriptional imbalance. Thus, research directed at expanding our present understanding of transcriptional co-repressors could impact the future development of new cancer diagnostics, prognostics, and therapies. In this review, our current understanding of the CtBP co-repressors, 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 pro-tumorigenic 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 (EMT). As a transcriptional regulator of broad developmental processes capable of promoting malignant growth in adult tissues, therapeutically targeting the CtBP1 co-repressor has the potential to be an effective method for the treatment of diverse tumor types. While efforts to develop CtBP1 inhibitors are still in the early stages, the current progress and the future perspectives of therapeutically targeting this transcriptional co-repressor are also discussed.