癌变
生物
转移
癌症研究
癌症
纤维连接蛋白
整合素
细胞
细胞生物学
遗传学
作者
Zhenghao Lu,Ailing Zhong,Hongyu Liu,Mengsha Zhang,Xuelan Chen,Xiangyu Pan,Manli Wang,Xintong Deng,Limin Gao,Lin-Yong Zhao,Jian Wang,Yi Yang,Qi Zhang,Baohong Wu,Jianan Zheng,Yi-Gao Wang,Xiao-Hai Song,Kai Liu,Weihan Zhang,Xiao‐Long Chen
出处
期刊:Cell Reports
[Cell Press]
日期:2022-10-01
卷期号:41 (3): 111482-111482
被引量:12
标识
DOI:10.1016/j.celrep.2022.111482
摘要
Gastric cancer (GC) is one of the most frequent and lethal malignancies in the world. However, our understanding of the mechanisms underlying its initiation and progression is limited. Here, we generate a series of primary GC models in mice with genome-edited gastric organoids, which elucidate the genetic drivers for sequential transformation from dysplasia to well-differentiated and poorly differentiated GC. Further, we find that the orthotopic GC, but not the subcutaneous GC even with the same genetic drivers, display remote metastasis, suggesting critical roles of the microenvironment in GC metastasis. Through single-cell RNA-seq analyses and functional studies, we show that the interaction between fibronectin 1 on stomach-specific macrophages and integrin a6β4 on GC cells promotes remote metastases. Taken together, our studies propose a strategy to model GC and dissect the genetic and microenvironmental factors driving the full-range gastric tumorigenesis.
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