4.5 Article

CXCL12/CXCR4 facilitates perineural invasion via induction of the Twist/S100A4 axis in salivary adenoid cystic carcinoma

期刊

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 16, 页码 7901-7912

出版社

WILEY
DOI: 10.1111/jcmm.16713

关键词

CXCL12; CXCR4; perineural invasion (PNI); salivary adenoid cystic carcinoma (SACC); Schwann cell

资金

  1. National Natural Science Foundation of China [81972542, 82073000]
  2. National Science Foundation of Sichuan Province [2020JDRC0018, 2020YFS0171]
  3. Natural Science Foundation of Shandong Province [ZR2018BH026]
  4. Clinical Research Project of West China Hospital of Stomatology, Sichuan University [LCYJ2019-8]
  5. Exploration and Research Projects of West China College of Stomatoloy, Sichuan University [LCYJ2020-YJ-1]

向作者/读者索取更多资源

The study revealed that activation of the CXCL12/CXCR4 axis in SACC may promote perineural invasion (PNI) by inducing tumor cells to differentiate towards Schwann-like cells through the Twist/S100A4 axis, accelerating cancer progression.
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.

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