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


CONCLUSIONS
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.
Department of Otorhinolaryngology, Head and Neck Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
Kaile
K
Wu
Bing
B
Shen
Feifei
F
Jiang
Lin
L
Xia
Taotao
T
Fan
Maolin
M
Qin
Lianqiang
L
Yang
Jizheng
J
Guo
Yifan
Y
Li
Min
M
Zhu
Juan
J
Du
Yehai
Y
Liu
D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051901:Smad4 Protein / Q000378:metabolism; D016019:Survival Analysis; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D002118:Calcium; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D051901:Smad4 Protein; D050396:TRPP Cation Channels