Department of Pathology, Xuzhou Medical University, Xuzhou, 221004, China.
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China.
Mol Biol Rep. 2023 Oct;50(10):7955-7965. doi: 10.1007/s11033-023-08662-4. Epub 2023 Aug 3.
Tetraspanin 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.
Our 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.
Our 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.
跨膜糖蛋白四旋蛋白 8（TSPAN8）参与多种病理状况，包括人类恶性肿瘤。然而，TSPAN8 在促进胃癌（GC）进展中的作用及其潜在机制尚未完全阐明。
我们的研究发现 TSPAN8 在 GC 组织中的表达明显升高。我们还观察到 TSPAN8 高表达与 GC 的各种临床病理特征之间存在正相关，包括肿瘤分化、浸润深度、淋巴结转移和临床分期。此外，TSPAN8 表达升高提示预后不良。功能上，我们观察到 TSPAN8 的敲低显著减弱，而过表达 TSPAN8 则促进 GC 细胞迁移和侵袭。在体内实验中，TSPAN8 的敲低抑制了裸鼠肺转移。我们进一步探讨了 TSPAN8 的潜在机制，发现它通过加速 EGFR 和 AKT 的磷酸化来调节 GC 细胞中 EGFR 的表达。
我们的研究表明，TSPAN8 通过激活 EGFR/AKT 通路在促进肿瘤转移中发挥重要作用，表明它可能成为治疗胃癌的有前途的靶点。
