TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer
TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer
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DOI：
10.1007/s11033-023-08662-4
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发表时间：
2023-08
影响因子：
2.8
通讯作者：
Lin Zhang;Yuting Xu;Enmin Cai;Maojin Zheng;Lei Liu;Qingling Wang;Shibao Li
中科院分区：
文献类型：
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作者：
Lin Zhang;Yuting Xu;Enmin Cai;Maojin Zheng;Lei Liu;Qingling Wang;Shibao Li
研究背景四跨膜蛋白8（Tetraspanin 8，TSPAN 8）是一种跨膜糖蛋白，与包括人类恶性肿瘤在内的多种病理状态密切相关。然而，TSPAN 8在促进胃癌（GC）进展中的作用和潜在机制尚未完全了解。方法和结果我们的研究发现，TSPAN 8在GC组织中的表达显著升高。我们还观察到TSPAN 8的高表达与胃癌的各种临床病理特征，包括肿瘤分化、浸润深度、淋巴结转移和临床分期呈正相关。此外，升高的TSPAN 8表达指示不良预后。在功能上，我们观察到TSPAN 8的敲低显著减弱，而TSPAN 8的过表达促进GC细胞迁移和侵袭。在体内实验中，TSPAN 8的敲低抑制了裸鼠中的肺转移。我们进一步探讨了TSPAN 8的作用机制，发现它通过促进EGFR和AKT的磷酸化来调节胃癌细胞EGFR的表达。结论TSPAN 8通过激活EGFR/AKT通路，在促进肿瘤转移中发挥重要作用，提示它可能成为胃癌治疗的新靶点。
BackgroundTetraspanin 8 (TSPAN8), a transmembrane glycoprotein, is implicated in various pathological conditions including human malignancies. However, the roles and underlying mechanisms of TSPAN8 in promoting gastric cancer(GC) progression are yet to be fully understood.Methods and resultsOur study found that TSPAN8 expression was significantly elevated in GC tissues. We also observed a positive correlation between high TSPAN8 expression and various clinicopathological characteristics of GC, including tumor differentiation, invasion depth, lymph node metastasis, and clinical stage. Moreover, the elevated TSPAN8 expression was indicative of poor prognosis. Functionally, we observed that knockdown of TSPAN8 significantly attenuated while overexpression of TSPAN8 promoted GC cell migration and invasion. In vivo experiments, knockdown of TSPAN8 suppressed lung metastasis in nude mice. We further explored the underlying mechanisms of TSPAN8 and found that it regulated EGFR expression in GC cells by accelerating phosphorylation of EGFR and AKT.ConclusionsOur study reveals that TSPAN8 plays a significant role in promoting tumor metastasis by activating the EGFR/AKT pathway, indicating that it may serve as a promising therapeutic target of gastric cancer.