Institute of Translational Pharmacology (IFT), National Research Council (CNR), Palermo, via Ugo La Malfa 153, 90146, Italy.
Carcinogenesis. 2024 Sep 11;45(9):621-629. doi: 10.1093/carcin/bgae049.
Notch-1 signaling plays a crucial role in stem cell maintenance and in repair mechanisms in various mucosal surfaces, including airway mucosa. Persistent injury can induce an aberrant activation of Notch-1 signaling in stem cells leading to an increased risk of cancer initiation and progression. Chronic inflammatory respiratory disorders, including chronic obstructive pulmonary disease (COPD) is associated with both overactivation of Notch-1 signaling and increased lung cancer risk. Increased oxidative stress, also due to cigarette smoke, can further contribute to promote cancer initiation and progression by amplifying inflammatory responses, by activating the Notch-1 signaling, and by blocking regulatory mechanisms that inhibit the growth capacity of stem cells. This review offers a comprehensive overview of the effects of aberrant Notch-1 signaling activation in stem cells and of increased oxidative stress in lung cancer. The putative role of natural compounds with antioxidant properties is also described.
Notch-1 信号通路在干细胞维持和多种黏膜表面（包括气道黏膜）的修复机制中起着至关重要的作用。持续的损伤会导致干细胞中 Notch-1 信号通路的异常激活，从而增加癌症发生和进展的风险。慢性炎症性呼吸系统疾病，包括慢性阻塞性肺疾病（COPD），与 Notch-1 信号通路的过度激活和肺癌风险增加有关。氧化应激的增加，也由于香烟烟雾的原因，通过放大炎症反应、激活 Notch-1 信号通路以及阻断抑制干细胞生长能力的调节机制，进一步促进癌症的发生和发展。这篇综述全面概述了异常 Notch-1 信号通路激活对干细胞和肺癌中氧化应激增加的影响。还描述了具有抗氧化特性的天然化合物的潜在作用。
