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 - Funding Information:
We thank r . Dake Huang in the comprehensive Laboratory of School of Basic ?edical Sciences in Anhui ?edical University for technical support. This work was supported by Grants from National Natural Science Foundation of China (Grant No. 稃猃甃礃猃球稃瘁 稃猃眃礃爃瘃爃甂I; Anhui Provincial Natural Science Foundation (Grant No. 猃瘃爃稃爃稃眀ကH 猃眃礂I; Science and Technology Research Project of Anhui Province (Grant No. 猃眃爃猃爃瘃猃猃瘃礂I; Young Prominent Investigator Supporting Program from Anhui ?edical University; Overseas Scholars Start Fund from Department of Human Resources and Social Security of Anhui Province.
Funding Information:
We thank Mr. Dake Huang in the comprehensive Laboratory of School of Basic Medical Sciences in Anhui Medical University for technical support. This work was supported by Grants from National Natural Science Foundation of China (Grant No. 81371284, 81570403); Anhui Provincial Natural Science Foundation (Grant No. 1408085MH157); Science and Technology Research Project of Anhui Province (Grant No. 1501041147); Young Prominent Investigator Supporting Program from Anhui Medical University; Overseas Scholars Start Fund from Department of Human Resources and Social Security of Anhui Province.
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 -