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CXCL12/CXCR4 facilitates perineural invasion via induction of the Twist/S100A4 axis in salivary adenoid cystic carcinoma |
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| Authors: | Mei Zhang Min Zheng Li Dai Wei-long Zhang Hua-yang Fan Xiang-hua Yu Xin Pang Peng Liao Bing-jun Chen Sha-sha Wang Ming-xin Cao Xiang-rui Ma Xin-hua Liang Ya-ling Tang |
| Institution: | 1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation (equal), Formal analysis (equal), ?Investigation (equal), Methodology (equal), Visualization (equal), Writing - original draft (equal);2. Department of Stomatology, Zhoushan Hospital, Wenzhou Medical University. Zhoushan, Zhejiang, China Contribution: ?Investigation (equal), Methodology (equal), Visualization (equal);3. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China Contribution: Data curation (equal), Formal analysis (equal);4. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China Contribution: Data curation (equal), Formal analysis (equal);5. Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, China Contribution: Writing - review & editing (equal);6. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China;7. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China |
| Abstract: | The activation of CXCL12/CXCR4 axis participated in the progression of multiple cancers, but potential effect in terms of perineural invasion (PNI) in SACC remained ambiguous. In this study, we identified that CXCL12 substantially expressed in nerve cells. CXCR4 strikingly expressed in tumour cells, and CXCR4 expression was closely associated with the level of EMT-associated proteins and Schwann cell hallmarks at nerve invasion frontier in SACC. Activation of CXCL12/CXCR4 axis could promote PNI and up-regulate relative genes of EMT and Schwann cell hallmarks both in vitro and in vivo, which could be inhibited by Twist silence. After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann-like cell through Twist/S100A4 axis in SACC. |
| Keywords: | CXCL12/CXCR4 perineural invasion (PNI) salivary adenoid cystic carcinoma (SACC) Schwann cell |