Axon guidance molecule semaphorin3A is a novel tumor suppressor in head and neck squamous cell carcinoma.
Axon guidance molecule semaphorin3A is a novel tumor suppressor in head and neck squamous cell carcinoma.
复制标题
轴突引导分子 semaphorin3A 是头颈部鳞状细胞癌的新型肿瘤抑制因子。
DOI：
10.18632/oncotarget.6831
复制
发表时间：
2016-02-02
期刊：
影响因子：
--
通讯作者：
Song X
中科院分区：
文献类型：
--
作者：
Wang Z;Chen J;Zhang W;Zheng Y;Wang Z;Liu L;Wu H;Ye J;Zhang W;Qi B;Wu Y;Song X
Semaphorin 3A（SEMA 3A）是神经系统中的轴突导向分子，在肿瘤发生中起抑制作用。在这里，我们研究了SEMA 3A在头颈部鳞状细胞癌（HNSCC）的表达模式和生物学作用的功能获得性测定使用腺病毒转染和重组人SEMA 3A蛋白。此外，我们探索了SEMA 3A对HNSCC的体内治疗效果。我们发现SEMA 3A的低表达与较短的总生存期相关，并且在HNSCC患者中具有独立的预后重要性。SEMA 3A基因表达和重组蛋白表达均能抑制细胞增殖和集落形成，诱导细胞凋亡，并伴有细胞周期蛋白E、细胞周期蛋白D、细胞周期蛋白激酶2、细胞周期蛋白激酶4和细胞周期蛋白激酶6的表达降低，P21、P27的表达增加，caspase-5和caspase-7的活化。此外，SEMA 3A的过表达抑制了迁移、侵袭和上皮-间质转化，部分原因是抑制了HNSCC细胞系中的NF-κB和SNAI 2。此外，肿瘤内SEMA 3A递送在异种移植物模型中显著停滞肿瘤生长。综上所述，我们的结果表明，SEMA 3A在HNSCC肿瘤发生过程中充当肿瘤抑制因子，并且是治疗HNSCC的新靶点。
Semaphorin3A (SEMA3A), an axon guidance molecule in the nervous system, plays an inhibitory role in oncogenesis. Here, we investigated the expression pattern and biological roles of SEMA3A in head and neck squamous cell carcinoma (HNSCC) by gain-of-function assays using adenovirus transfection and recombinant human SEMA3A protein. In addition, we explored the therapeutic efficacy of SEMA3A against HNSCC in vivo. We found that lower expression of SEMA3A correlated with shorter overall survival and had independent prognostic importance in patients with HNSCC. Both genetic and recombinant SEMA3A protein inhibited cell proliferation and colony formation and induced apoptosis, accompanied by decreased cyclin E, cyclin D, CDK2, CDK4 and CDK6 and increased P21, P27, activated caspase-5 and caspase-7. Moreover, over-expression of SEMA3A suppressed migration, invasion and epithelial-to-mesenchymal transition due in part to the inhibition of NF-κB and SNAI2 in HNSCC cell lines. Furthermore, intratumoral SEMA3A delivery significantly stagnated tumor growth in a xenograft model. Taken together, our results indicate that SEMA3A serves as a tumor suppressor during HNSCC tumorigenesis and a new target for the treatment of HNSCC.