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

Kaile Wu, Bing Shen, Feifei Jiang, Lin Xia, Taotao Fan, Maolin Qin, Lianqiang Yang, Jizheng Guo, Yifan Li, Min Zhu, Juan Du, Yehai Liu

    Research output: Contribution to journalArticlepeer-review

    20 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)2203-2215
    Number of pages13
    JournalCellular Physiology and Biochemistry
    Volume39
    Issue number6
    DOIs
    StatePublished - Nov 1 2016

    Keywords

    • Epithelial-mesenchymal transition
    • Laryngeal squamous cell carcinoma
    • Metastasis
    • STAT3
    • Smad4
    • TRPP2

    ASJC Scopus subject areas

    • Physiology

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