title: Axon guidance molecule semaphorin3A is a novel tumor suppressor in head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Zilu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Laikui
authors.initials: L
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Heming
authors.initials: H
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qi
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Yunong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.|Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Song
mesh_terms: D000818:Animals; D000071437:Axon Guidance; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011897:Random Allocation; D040121:Semaphorin-3A / Q000008:administration & dosage / Q000096:biosynthesis* / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C108639:SEMA3A protein, human; D040121:Semaphorin-3A
keywords: HNSCC; NF-kappaB; Snail; apoptosis; semaphorin3A