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技术文章
文献引用产品：人皮肤成纤维细胞HDF-a
点击次数：620 发布时间：2026/6/5 8:37:59
文章标题：In Vivo CRISPR Screening Identifies the Glutamate Receptor GRIA2 as Promoting Peritoneal Metastasis of Gastric Cancer via Calcium-Dependent β-Catenin Activation
作者列表：Jie Sun, Xu Yang, Wenchao Jiang, Chengbo Ji, Yingying Wu, Haoyu Sun, Xinyou Liu, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Junjie Zhao, Yuanyuan Ruan, Haojie Li, Xuefei Wang
影响因子：14.1
期刊：Advanced Science
发表时间：2026-3-10
DOI:10.1002/advs.202521746
文献主题：ABSTRACT
Peritoneal ｍmbedstasis is the most lethal manifestation of gastric cancer, with a median survival of less than one year, highlighting the need for new therapeutic targets. Through an in vivo genome-wide CRISPR/Cas9 screen, we identified GRIA2, an AMPA-type glutamate receptor subunit, as a key driver of peritoneal ｍmbedstasis. GRIA2 promotes gastric cancer cell migration, invasion, stemness, and adhesion to mesothelial cells in a glutamate-dependent manner. Mechanistically, glutamate activates GRIA2, enhancing its interaction with GSK-3β and inducing calcium influx, inhibiting GSK-3β kinase activity and stabilizing β-catenin, thereby activating the Wnt/β-catenin signaling pathway. Single-cell RNA sequencing revealed that cancer-associated fibroblasts are the primary source of glutamate in the peritoneal microenvironment, which establishes a paracrine axis that enhances GRIA2-driven ｍmbedstasis. Pharmacological inhibition of AMPA receptors with NBQX and Selurampanel suppressed peritoneal ｍmbedstasis in both cell line-derived and patient-derived organoid xenograft (PDOX) mouse models. In clinical analysis, GRIA2 expression in peritoneal ｍmbedstases correlated with the levels of β-catenin and phosphorylated GSK-3β (serine 9), with high GRIA2 expression predicting poor prognosis. These findings suggest that GRIA2 is a novel therapeutic target, and AMPA receptor antagonists are promising agents for treating gastric cancer peritoneal ｍmbedstasis.
原创作者：上海雅吉生物科技有限公司
