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
相关论文
共 37 条
  • [11] Levels of TGF-α and EGFR protein in head and neck squamous cell carcinoma and patient survival
    Grandis, JR
    Melhem, MF
    Gooding, WE
    Day, R
    Holst, VA
    Wagener, MM
    Drenning, SD
    Tweardy, DJ
    [J]. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (11): : 824 - 832
  • [12] Jin YT, 1998, CANCER, V82, P2159, DOI 10.1002/(SICI)1097-0142(19980601)82:11<2159::AID-CNCR10>3.0.CO
  • [13] 2-T
  • [14] N-myc downstream-regulated gene 2 (NDRG2) suppresses the epithelial-mesenchymal transition (EMT) in breast cancer cells via STAT3/Snail signaling
    Kim, Myung-Jin
    Lim, Jihyun
    Yang, Young
    Lee, Myeong-Sok
    Lim, Jong-Seok
    [J]. CANCER LETTERS, 2014, 354 (01) : 33 - 42
  • [15] The molecular biology of head and neck cancer
    Leemans, C. Rene
    Braakhuis, Boudewijn J. M.
    Brakenhoff, Ruud H.
    [J]. NATURE REVIEWS CANCER, 2011, 11 (01) : 9 - 22
  • [16] Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression
    Lo, Hui-Wen
    Hsu, Sheng-Chieh
    Xia, Weiya
    Cao, Xinyu
    Shih, Jin-Yuan
    Wei, Yongkun
    Abbruzzese, James L.
    Hortobagyi, Gabriel N.
    Hung, Men-Chie
    [J]. CANCER RESEARCH, 2007, 67 (19) : 9066 - 9076
  • [17] PKD2 functions as an epidermal growth factor-activated plasma membrane channel
    Ma, R
    Li, WP
    Rundle, D
    Kong, J
    Akbarali, HI
    Tsiokas, L
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (18) : 8285 - 8298
  • [18] Menè P, 2013, CURR TOP MED CHEM, V13, P386
  • [19] PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein
    Mochizuki, T
    Wu, GQ
    Hayashi, T
    Xenophontos, SL
    Veldhuisen, B
    Saris, JJ
    Reynolds, DM
    Cai, YQ
    Gabow, PA
    Pierides, A
    Kimberling, WJ
    Breuning, MH
    Deltas, CC
    Peters, DJM
    Somlo, S
    [J]. SCIENCE, 1996, 272 (5266) : 1339 - 1342
  • [20] Smooth muscle cell transient receptor potential polycystin-2 (TRPP2) channels contribute to the myogenic response in cerebral arteries
    Narayanan, Damodaran
    Bulley, Simon
    Leo, M. Dennis
    Burris, Sarah K.
    Gabrick, Kyle S.
    Boop, Frederick A.
    Jaggar, Jonathan H.
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 2013, 591 (20): : 5031 - 5046