Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Oncogene. 2021 Mar;40(9):1555-1569. doi: 10.1038/s41388-020-01587-3. Epub 2020 Dec 15.
Colorectal cancer (CRC) is a major cause of cancer mortality worldwide, however, the molecular mechanisms underlying the pathogenesis of CRC remain largely unclear. Recent studies have revealed crucial roles of transcription factors in CRC development. Transcription factors essential for the regulation of gene expression by interacting with transcription corepressor/enhancer complexes and they orchestrate downstream signal transduction. Deregulation of transcription factors is a frequent occurrence in CRC, and the accompanying drastic changes in gene expression profiles play fundamental roles in multistep process of tumorigenesis, from cellular transformation, disease progression to metastatic disease. Herein, we summarized current and emerging key transcription factors that participate in CRC tumorigenesis, and highlighted their oncogenic or tumor suppressive functions. Moreover, we presented critical transcription factors of CRC, emphasized the major molecular mechanisms underlying their effect on signal cascades associated with tumorigenesis, and summarized of their potential as molecular biomarkers for CRC prognosis therapeutic response, as well as drug targets for CRC treatment. A better understanding of transcription factors involved in the development of CRC will provide new insights into the pathological mechanisms and reveal novel prognostic biomarkers and therapeutic strategies for CRC.
结直肠癌(CRC)是全球癌症死亡的主要原因,但 CRC 发病机制的分子机制在很大程度上仍不清楚。最近的研究揭示了转录因子在 CRC 发展中的关键作用。转录因子通过与转录核心抑制子/增强子复合物相互作用,对于基因表达的调控至关重要,它们协调下游信号转导。转录因子的失调在 CRC 中经常发生,伴随而来的基因表达谱的剧烈变化在肿瘤发生的多步骤过程中发挥着重要作用,从细胞转化、疾病进展到转移性疾病。本文总结了目前和新兴的参与 CRC 肿瘤发生的关键转录因子,并强调了它们的致癌或肿瘤抑制功能。此外,我们介绍了 CRC 的关键转录因子,强调了它们对与肿瘤发生相关的信号级联的主要分子机制,并总结了它们作为 CRC 预后、治疗反应的分子生物标志物以及 CRC 治疗的药物靶点的潜力。深入了解参与 CRC 发展的转录因子将为病理机制提供新的见解,并揭示 CRC 的新的预后生物标志物和治疗策略。