TY - JOUR
T1 - TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma
AU - Wu, Kaile
AU - Shen, Bing
AU - Jiang, Feifei
AU - Xia, Lin
AU - Fan, Taotao
AU - Qin, Maolin
AU - Yang, Lianqiang
AU - Guo, Jizheng
AU - Li, Yifan
AU - Zhu, Min
AU - Du, Juan
AU - Liu, Yehai
N1 - Publisher Copyright:
© 2016 The Author(s) Published by S. Karger AG, Basel.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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, Ca 2+ 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 Ca 2+ 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.
AB - 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, Ca 2+ 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 Ca 2+ 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.
KW - Epithelial-mesenchymal transition
KW - Laryngeal squamous cell carcinoma
KW - Metastasis
KW - STAT3
KW - Smad4
KW - TRPP2
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U2 - 10.1159/000447914
DO - 10.1159/000447914
M3 - Article
C2 - 27832627
AN - SCOPUS:84994742953
SN - 1015-8987
VL - 39
SP - 2203
EP - 2215
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
IS - 6
ER -