TSPAN8 调节 EGFR/AKT 通路以增强胃癌的转移。
TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer.
发表日期:2023 Aug 03
作者:
Lin Zhang, Yuting Xu, Enmin Cai, Maojin Zheng, Lei Liu, Qingling Wang, Shibao Li
来源:
Cellular & Molecular Immunology
摘要:
翻译:Tetraspanin 8(TSPAN8)是一种跨膜糖蛋白,与多种病理条件相关,包括人类恶性肿瘤。然而,目前对TSPAN8在促进胃癌(GC)进程中的作用和潜在机制尚不完全了解。我们的研究发现,在GC组织中,TSPAN8的表达显著增加。我们还观察到高表达的TSPAN8与GC的多种临床病理特征呈正相关,包括肿瘤分化、浸润深度、淋巴结转移和临床分期。此外,TSPAN8的高表达预示着较差的预后。在功能上,我们观察到TSPAN8的敲低显著减弱了GC细胞的迁移和侵袭能力,而TSPAN8的过表达则促进了细胞迁移和侵袭。在体内实验中,敲低TSPAN8抑制了裸鼠的肺转移。我们进一步研究了TSPAN8的潜在机制,发现它通过加速EGFR和AKT的磷酸化来调节GC细胞中的EGFR表达。我们的研究揭示了TSPAN8在通过激活EGFR/AKT通路促进肿瘤转移中的重要作用,表明它可能是胃癌的一个有希望的治疗靶点。© 2023. 作者等专属授权给Springer Nature B.V.
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.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.