TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma

被引:39
|
作者
Wu, Kaile [1 ]
Shen, Bing [2 ]
Jiang, Feifei [2 ,3 ]
Xia, Lin [2 ]
Fan, Taotao [2 ]
Qin, Maolin [1 ]
Yang, Lianqiang [4 ]
Guo, Jizheng [2 ]
Li, Yifan [1 ]
Zhu, Min [5 ]
Du, Juan [2 ]
Liu, Yehai [1 ]
机构
[1] Anhui Med Univ, Dept Otorhinolaryngol Head & Neck Surg, Affiliated Hosp 1, 218 Jixi Rd, Hefei 230022, Anhui, Peoples R China
[2] Anhui Med Univ, Sch Basic Med Sci, Dept Physiol, Hefei, Peoples R China
[3] Peoples Hosp Bozhou, Dept Pediat, Bozhou, Peoples R China
[4] Anhui Univ, Sch Math Sci, Dept Math, Hefei, Peoples R China
[5] Chinese Acad Sci, Hefei Inst Sci, Hefei, Peoples R China
基金
中国国家自然科学基金;
关键词
TRPP2; Laryngeal squamous cell carcinoma; Epithelial-mesenchymal transition; Metastasis; Smad4; STAT3; BREAST-CANCER CELLS; TGF-BETA; KIDNEY-DISEASE; EMT; CHANNELS; INVASION; GENE; PKD2; HEAD; ACTIVATION;
D O I
10.1159/000447914
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aim: Surgery and chemotherapy treatments of human laryngeal squamous cell carcinoma (HLSCC) may fail due to metastasis, in which epithelial-mesenchymal transition (EMT) plays an important role. TRPP2, a nonselective cation channel, is expressed in various cell types and participates in many biological processes. Here, we show that TRPP2 enhanced metastasis by regulating EMT. Methods: We used immunohistochemistry, western blotting, Ca2+ imaging, transwell and wound healing assays to investigate TRPP2 expression levels in HLSCC tissue, and the role of TRPP2 in invasion and metastasis of a human laryngocarcinoma cell line (Hep2 cell). Results: We found that TRPP2 protein expression levels were significantly increased in HLSCC tissue; higher TRPP2 levels were associated with decreased patient survival time and degree of differentiation and advanced clinical stage. Knockdown of TRPP2 by transfection with TRPP2 siRNA markedly suppressed ATP-induced Ca2+ release, wound healing, and cell invasion in Hep2 cells. Moreover, TRPP2 siRNA significantly decreased vimentin expression but increased E-cadherin expression in Hep2 cells. In the EMT signalling pathway, TRPP2 siRNA significantly decreased Smad4, STAT3, SNAIL, SLUG and TWIST expression in Hep2 cells. Conclusion: We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC. (C) 2016 The Author(s) Published by S. Karger AG, Basel.
引用
收藏
页码:2203 / 2215
页数:13
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