College of Life Sciences, Shaanxi Normal University, Xi'an, 710119, Shaanxi, China.
College of P.E and Sports, Beijing Normal University, Beijing, 100875, China.
J Cancer Res Clin Oncol. 2023 Sep;149(11):8495-8505. doi: 10.1007/s00432-023-04767-2. Epub 2023 Apr 24.
Gastric cancer (GC) remains a global challenge due to its high morbidity and mortality rates especially in Asia as well as poor response to treatment. As a member of the adhesion protein family and transmembrane glycoprotein, EpCAM expressed excessively in cancer cells including GC cells. The database assay showed that EpCAM is excessively expressed and easily mutated in cancers, especially in early stage of GC.
To explore the roles EpCAM plays in oncogenesis and progression of GC, the expression of EpCAM was deleted in GC cells with CRISPR/Cas9 method, and then the changes of cell proliferation, apoptosis, motility and motility associated microstructures in EpCAM-deleted GC cells (EpCAM-/-SGC7901) were detected to evaluate the rules EpCAM played.
The results showed that EpCAM deletion caused cell proliferation, motility and the development of motility-relevant microstructures inhibited significantly, apoptotic trend and contact inhibition enhanced in EpCAM-deleted GC cells. The results of western blot suggested that EpCAM modulates the expression of epithelial/endothelial mesenchymal transition (EMT) correlated genes. All results as above indicated that EpCAM plays important roles to enhance the oncogenesis, malignancy and progression as a GC enhancer.
Combining our results and published data together, the interaction of EpCAM with other proteins was also discussed and concluded in the discussion. Our results support that EpCAM can be considered as a novel target for the diagnosis and therapy of GC in future.
胃癌（GC）仍然是一个全球性的挑战，因为它的发病率和死亡率都很高，尤其是在亚洲，而且对治疗的反应也很差。EpCAM 作为黏附蛋白家族和跨膜糖蛋白的成员，在包括 GC 细胞在内的癌细胞中过度表达。数据库检测表明，EpCAM 在癌症中过度表达且容易突变，尤其是在 GC 的早期阶段。
为了探讨 EpCAM 在 GC 发生和发展中的作用，我们使用 CRISPR/Cas9 方法删除 GC 细胞中的 EpCAM 表达，然后检测 EpCAM 缺失的 GC 细胞（EpCAM-/-SGC7901）中细胞增殖、凋亡、迁移和迁移相关的微结构的变化，以评估 EpCAM 所起的作用规则。
结果表明，EpCAM 缺失导致细胞增殖、迁移和迁移相关的微结构的发育明显受到抑制，凋亡趋势和接触抑制增强。Western blot 的结果表明，EpCAM 调节上皮/内皮间充质转化（EMT）相关基因的表达。所有上述结果表明，EpCAM 作为 GC 增强子，通过增强肿瘤发生、恶性程度和进展来发挥重要作用。
结合我们的结果和已发表的数据，我们在讨论中还讨论并总结了 EpCAM 与其他蛋白质的相互作用。我们的研究结果表明，EpCAM 可以作为未来 GC 诊断和治疗的一个新靶点。
