Open AccessCXCL12/CXCR4 facilitates perineural invasion via induction of the Twist/S100A4 axis in salivary adenoid cystic carcinoma
Author(s) -
Zhang Mei,
Zheng Min,
Dai Li,
Zhang Weilong,
Fan Huayang,
Yu Xianghua,
Pang Xin,
Liao Peng,
Chen Bingjun,
Wang Shasha,
Cao Mingxin,
Ma Xiangrui,
Liang Xinhua,
Tang Yaling
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16713
Subject(s) - perineural invasion , adenoid cystic carcinoma , cxcr4 , gene knockdown , cancer research , pathology , biology , cell , microbiology and biotechnology , medicine , cancer , carcinoma , chemokine , cell culture , immunology , genetics , immune system
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.