Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China.
Department of Geriatrics Ward 2, The First Hospital of Lanzhou University, Lanzhou 730000, China.
Aging (Albany NY). 2024 Aug 21;16(16):11893-11903. doi: 10.18632/aging.206061.
To explore the underlying molecular mechanism of Notch1/cadherin 5 (CDH5) pathway in modulating in cell malignant behaviors of gastric cancer (GC).
We performed bioinformatic analyses to screen the potential target genes of Notch1 from cadherins in GC. Western blot and RT-PCR were conducted to detect CDH5 expression in GC tissues and cells. We utilized chromatin immunoprecipitation (CHIP) assays to assess the interaction of Notch1 with CDH5 gene. The effects of Notch1/CDH5 axis on the proliferation, invasion, migration and vasculogenic mimicry in GC cells were evaluated by EdU, wound healing, transwell, and tubule formation assays.
Significantly increased CDH5 expression was found in GC tissues compared with paracancerous tissues and associated to clinical stage and poor overall survival (OS) in patients with GC. Notch1 positively regulate the expression of CDH5 in GC cells. CHIP assays validated that CDH5 was a direct target of Notch1. In addition, Notch1 upregulation enhanced the proliferation, migration, invasion and vasculogenic mimicry capacity of GC cells, which could be attenuated by CDH5 silencing.
These results indicated Notch1 upregulation enhanced GC malignant behaviors by triggering CDH5, suggesting that targeting Notch1/CDH5 axis could be a potential therapeutic strategy for GC progression.
探讨 Notch1/钙黏蛋白 5（CDH5）通路在调控胃癌（GC）细胞恶性行为中的潜在分子机制。
我们进行了生物信息学分析，以筛选 GC 中 Notch1 与钙黏蛋白的潜在靶基因。采用 Western blot 和 RT-PCR 检测 GC 组织和细胞中 CDH5 的表达。利用染色质免疫沉淀（CHIP）实验评估 Notch1 与 CDH5 基因的相互作用。通过 EdU、划痕愈合、Transwell 和管腔形成实验评估 Notch1/CDH5 轴对 GC 细胞增殖、侵袭、迁移和血管生成拟态的影响。
与癌旁组织相比，GC 组织中 CDH5 的表达明显增加，且与 GC 患者的临床分期和总体生存（OS）不良相关。Notch1 正向调控 GC 细胞中 CDH5 的表达。CHIP 实验验证了 CDH5 是 Notch1 的直接靶基因。此外，Notch1 的上调增强了 GC 细胞的增殖、迁移、侵袭和血管生成拟态能力，而 CDH5 的沉默则可减弱这种能力。
这些结果表明，Notch1 的上调通过触发 CDH5 增强了 GC 的恶性行为，提示靶向 Notch1/CDH5 轴可能是 GC 进展的一种潜在治疗策略。
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