Axon guidance molecule semaphorin3A is a novel tumor suppressor in head and neck squamous cell carcinoma
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Zhao Wang1,2, Jie Chen1,2, Wei Zhang1, Yang Zheng1,2, Zilu Wang1, Laikui Liu1, Heming Wu1,2, Jinhai Ye1,2, Wei Zhang3, Bing Qi3, Yunong Wu1,2, Xiaomeng Song1,2
1Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China
2Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China
3Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China
Xiaomeng Song, e-mail: [email protected]
Yunong Wu, e-mail: [email protected]
Keywords: semaphorin3A, HNSCC, apoptosis, NF-kappaB, Snail
Received: April 07, 2015 Accepted: December 28, 2015 Published: January 08, 2016
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.
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