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Updated: Mar 27, 2026

Three-Dimensional 3D Tumor Spheroid Invasion Assay
Published on: May 1, 2015
Axon guidance molecule semaphorin3A is a novel tumor suppressor in head and neck squamous cell carcinoma
Zhao Wang1,2, Jie Chen1,2, Wei Zhang1
1Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
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.
Insights
Semaphorin3A (SEMA3A) acts as a tumor suppressor in head and neck squamous cell carcinoma (HNSCC). Its restoration inhibits cancer growth and presents a potential therapeutic target for HNSCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Semaphorin3A (SEMA3A) is an axon guidance molecule with known roles in inhibiting oncogenesis.
- The specific role and therapeutic potential of SEMA3A in head and neck squamous cell carcinoma (HNSCC) remain to be fully elucidated.
Purpose of the Study:
- To investigate the expression pattern and biological functions of SEMA3A in HNSCC.
- To evaluate the therapeutic efficacy of SEMA3A as a potential treatment for HNSCC.
Main Methods:
- Gain-of-function assays using adenovirus transfection and recombinant SEMA3A protein.
- In vitro studies assessing cell proliferation, apoptosis, migration, invasion, and epithelial-to-mesenchymal transition (EMT).
- In vivo xenograft models to evaluate therapeutic efficacy.
Main Results:
- Lower SEMA3A expression correlated with shorter overall survival in HNSCC patients, indicating prognostic importance.
- SEMA3A overexpression inhibited HNSCC cell proliferation, colony formation, and induced apoptosis by modulating cell cycle and caspase proteins.
- SEMA3A suppressed migration, invasion, and EMT, partly via inhibition of NF-κB and SNAI2.
- Intratumoral SEMA3A delivery significantly inhibited tumor growth in vivo.
Conclusions:
- SEMA3A functions as a tumor suppressor in HNSCC tumorigenesis.
- SEMA3A demonstrates significant therapeutic potential and represents a novel therapeutic target for HNSCC.
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