School of Stomatology, Lanzhou University, Lanzhou, China.
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
Front Public Health. 2021 Feb 3;9:631118. doi: 10.3389/fpubh.2021.631118. eCollection 2021.
Oral cancer is a very aggressive disease with high rates of recurrence and metastasis. This study aimed at addressing how efficiently tongue cancer is suppressed after carbon ion irradiation. Here, the close relationship between upregulated expression of focal adhesion kinase (FAK) and high metastatic status in tongue squamous cell carcinoma patients was validated using bioinformatics and immunohistochemical analyses. Our data indicated that FAK suppression significantly enhanced the killing effect induced by irradiation in the tongue cancer cell line CAL27, as evidenced by increased apoptotic induction and reduced colony formation. More importantly, in FAK-deficient cells, carbon ion irradiation was shown to remarkably inhibit migration and invasion by delaying wound healing and slowing down motility. Further studies revealed that irradiation exposure caused disorganization of the actin cytoskeleton and reduced cell adhesive energy in FAK-deficient cells. Moreover, carbon ion treatment, in combination with FAK silencing, markedly blocked the phosphorylation levels of FAK, and paxillin, which partly contributed to the reduced motility of tongue squamous cell carcinoma CAL27 cells. Collectively, these results suggest that the prominent obstructing role of carbon ion irradiation in the growth inhibition and metastatic behavior of tumors, including attenuation of cell adhesiveness, motility, and invasiveness, could be distinctly modulated by FAK-mediated downstream pathways.
口腔癌是一种侵袭性很强的疾病，复发率和转移率都很高。本研究旨在探讨碳离子照射后舌癌的抑制效率。本研究通过生物信息学和免疫组织化学分析验证了粘着斑激酶（FAK）的上调表达与舌鳞癌细胞患者的高转移状态之间的密切关系。我们的数据表明，FAK 抑制显著增强了碳离子照射对舌癌细胞系 CAL27 的杀伤作用，这表现在诱导凋亡增加和集落形成减少。更重要的是，在 FAK 缺陷细胞中，碳离子照射通过延迟伤口愈合和减缓运动来显著抑制迁移和侵袭。进一步的研究表明，照射暴露导致 FAK 缺陷细胞中的肌动蛋白细胞骨架紊乱和细胞黏附能降低。此外，碳离子处理与 FAK 沉默联合使用，显著阻断了 FAK 和桩蛋白的磷酸化水平，这部分导致了舌鳞癌细胞 CAL27 运动能力的降低。综上所述，这些结果表明，碳离子照射在肿瘤生长抑制和转移行为中的显著阻断作用，包括细胞黏附性、运动性和侵袭性的减弱，可通过 FAK 介导的下游途径明显调节。
