Transcription is a core hallmark of cancer, wherein many different proteins assemble at specific sites in the nucleus and act in concert to transcribe functionally relevant genes. Central to this process are transcription factors that bind to their cognate DNA motifs on enhancers and super-enhancers to recruit cofactors, coactivators, and epigenetic modifiers, thereby inducing or repressing gene expression. Super-enhancers drive oncogenic transcription, to which cancer cells become highly addicted and confer tumor dependencies on super-enhancer-driven transcription machinery. Transcriptional condensates (TCs) are nuclear membrane-less assemblies of DNA-binding transcription factors, transcription co-activators, and the transcriptional machinery (such as RNA polymerases, non-coding RNAs) formed through liquid–liquid phase separation (LLPS). The function of transcriptionally active oncogenic proteins and their interplay with nucleic acids are carried out within these biomolecular condensates, allowing them to spatiotemporally regulate oncogene expression and lead to the induction and maintenance of cancer. With this growing understanding, specific inhibitors and strategies targeting TC assembly and activation should be considered promising therapeutic opportunities for treating various tumors, including hematological malignancies.
转录是癌症的核心标志之一，其中多种不同蛋白质在细胞核内特定位置组装并协同作用，转录功能相关的基因。这一过程的核心是转录因子，它们结合在增强子和超级增强子上的同源DNA基序，招募辅因子、共激活因子和表观遗传修饰因子，从而诱导或抑制基因表达。超级增强子驱动致癌转录，癌细胞对此高度依赖，并使肿瘤依赖于超级增强子驱动的转录机制。转录凝聚体是通过液-液相分离形成的无核膜组装体，由DNA结合转录因子、转录共激活因子以及转录机制（如RNA聚合酶、非编码RNA）组成。具有转录活性的致癌蛋白的功能及其与核酸的相互作用在这些生物分子凝聚体内进行，使其能够时空调控致癌基因表达，进而诱导和维持癌症。随着认识的不断深入，针对转录凝聚体组装和激活的特异性抑制剂及策略应被视为治疗包括血液恶性肿瘤在内的多种肿瘤的有前景的治疗机遇。
肿瘤(癌症)患者之家