State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Signal Transduct Target Ther. 2024 May 27;9(1):128. doi: 10.1038/s41392-024-01828-x.
Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.
Notch 信号通路以其在调控多细胞生物中的细胞命运、器官发育和组织稳态方面的作用而闻名，在进化过程中高度保守。Notch 受体及其配体是含有表皮生长因子样重复序列的跨膜蛋白，通常需要受体-配体相互作用来启动经典的 Notch 信号转导。越来越多的证据表明，Notch 信号通路在各种癌症类型中既是致癌因子，也是肿瘤抑制因子。该通路的失调促进了恶性肿瘤中的上皮-间充质转化和血管生成，与癌症的增殖、侵袭和转移密切相关。此外，Notch 信号通路有助于维持癌细胞中的干细胞样特性，从而增强癌症的侵袭性。Notch 信号通路在癌症代谢重编程和肿瘤微环境中的调节作用表明其在平衡致癌和肿瘤抑制效应方面发挥着关键作用。此外，Notch 信号通路与肿瘤细胞的化疗耐药性有关。因此，全面了解这些生物学过程对于开发针对 Notch 信号的创新治疗策略至关重要。本综述重点介绍了 Notch 信号通路在癌症中的研究进展，深入探讨了 Notch 信号调节在癌症发生和发展中的潜在机制。此外，该综述总结了针对 Notch 信号的药物临床试验用于癌症治疗，旨在为人类恶性肿瘤的治疗策略提供新的思路。
