Fusobacterium nucleatum promotes the early occurrence of esophageal cancer through upregulation of IL ‐32/ PRTN3 expression

作者：Jing Lei, Feng Xu, Chao Deng, Xubiao Nie, Li Zhong, Zhixuan Wu, Juan Li, Xiaoling Wu, Song He, Yongyu Chen · 发表于：Cancer Science · 年份：2023 · DOI：10.1111/cas.15787 · 被引用次数：39 · 研究领域：Esophageal Cancer Research and Treatment、Helicobacter pylori-related gastroenterology studies、Immune cells in cancer

Previous studies have shown that gastrointestinal microbiome is associated with the development of esophageal cancer, but the relationship and molecular mechanism between esophageal microbiota and the early development of esophageal cancer remain unclear. Here, we found that Lactobacillus, Escherichia-Shigella, Rikenellaceae-RC9-gut-group, Morganella, and Fusobacterium were more abundant in early-stage esophageal cancer (EEC) tissues compared with normal esophageal tissues. The abundance of bacteria such as Prevotella, Fusobacterium, Porphyromonas, Actinobacillus, and Neisseria in advanced esophageal cancer (AEC) was higher than that in EEC. Then, we further verified that Fusobacterium nucleatum (Fn) was enriched in EEC tissues and that its abundance increased with the progression of esophageal cancer by FISH and RT-PCR. Next, we demonstrated that Fn promoted the proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Finally, we confirmed that Fn promoted ESCC proliferation by upregulating the expression of interleukin (IL)-32/proteinase 3 (PRTN3) and then activating the PI3K/AKT signaling pathway. In conclusion, Fn promoted the early development of ESCC by upregulating the expression of IL-32/PRTN3 and thereby activating the PI3K/AKT signaling pathway. A better understanding of the molecular mechanism of Fn in early esophageal cancer may contribute to the development of early screening markers to diagnose ESCC and provide new targets for treatment.