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

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.

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Long noncoding RNA MYOSLID promotes invasion and metastasis by modulating the partial epithelial-mesenchymal transition program in head and neck squamous cell carcinoma

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1254-4 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 24

Author(s):

Hong-Gang Xiong ◽

Hao Li ◽

Yao Xiao ◽

Qi-Chao Yang ◽

Lei-Lei Yang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Epithelial Mesenchymal Transition ◽

Neck Squamous Cell Carcinoma ◽

Invasion And Metastasis ◽

Mesenchymal Transition

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Knockdown of Snail inhibits epithelial–mesenchymal transition of human laryngeal squamous cell carcinoma Hep-2 cells through the vitamin D receptor signaling pathway

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0039 ◽

2017 ◽

Vol 95 (6) ◽

pp. 672-678 ◽

Cited By ~ 7

Author(s):

Xue Zhao ◽

Dan Yu ◽

Jingpu Yang ◽

Kai Xue ◽

Yan Liu ◽

...

Keyword(s):

Vitamin D ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Vitamin D Receptor ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Integrin Subunit ◽

Mesenchymal Transition

It has been well documented that Snail plays a decisive role in various tumors. However, the direct effect of Snail on laryngeal squamous cell carcinoma (LSCC) has not been elaborated. In this study, we firstly detected the expression of Snail in 14 samples of patients with LSCC and found that its content was high in cancer tissues compared with adjacent tissues. Then we established LSCC Hep-2 cells with Snail silencing and validated the knockdown efficiency by Western blotting and real-time PCR. Results showed that silencing of Snail significantly inhibited the ability of adhesion, migration, and invasion of Hep-2 cells. Further study revealed that knockdown of Snail suppressed the epithelial–mesenchymal transition (EMT) process of Hep-2 cells, as evidenced by downregulation of matrix metallopeptidase (MMP)-2, MMP-9, integrin subunit beta 1 (ITGβ1), β-catenin, vimentin, N-cadherin, and fibronectin and upregulation of vitamin D receptor (VDR) and E-cadherin. Additionally, transfection with the small interfering RNA of VDR reversed the effect induced by Snail silencing in Hep-2 cells. Taken together, these results demonstrate that knockdown of Snail can inhibit the EMT process of LSCC cells through the VDR signaling pathway in vitro.

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Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

ISRN Oncology ◽

10.5402/2012/681469 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 21

Author(s):

Suttichai Krisanaprakornkit ◽

Anak Iamaroon

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Signaling Pathways ◽

Squamous Cell ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Large Body ◽

Invasion And Metastasis ◽

Mesenchymal Transition

Oral cancer is one of the drastic human cancers due to its aggressiveness and high mortality rate. Of all oral cancers, squamous cell carcinoma is the most common accounting for more than 90%. Epithelial-mesenchymal transition (EMT) is suggested to play an important role during cancer invasion and metastasis. Recently, emerging knowledge on EMT in carcinogenesis is explosive, tempting us to analyze previous studies on EMT in oral squamous cell carcinoma (OSCC). In this paper, we have first addressed the general molecular mechanisms of EMT, evidenced by alterations of cell morphology during EMT, the presence of cadherin switching, turning on and turning off of many specific genes, the activation of various signaling pathways, and so on. The remaining part of this paper will focus on recent findings of the investigations of EMT on OSCC. These include the evidence of EMT taking place in OSCC and the signaling pathways employed by OSCC cells during their invasion and metastasis. Collectively, with the large body of new knowledge on EMT in OSCC elaborated here, we are hopeful that targeting treatment for OSCC will be developed.

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MicroRNA-625 inhibits cell invasion and epithelial–mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma

Bioscience Reports ◽

10.1042/bsr20181882 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 4

Author(s):

Yuan Li ◽

Chenjuan Tao ◽

Lili Dai ◽

Caixia Cui ◽

Chaohui Chen ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Critical Role ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Expression Levels

AbstractIntroduction: Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive. The purpose of the present study is to investigate the expression profile and functional role of microRNA-625 (miR-625) in LSCC.Materials and methods: LSCC tissues and adjacent normal tissues were collected from 86 LSCC patients. The expression levels of miR-625 and SOX4 mRNA in tissues and cells were detected by RT-qPCR analysis. The expression levels of SOX4 and EMT-related proteins were detected by western blot analysis. In vitro cell proliferation, migration, and invasion were detected by MTT assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively. Dual-luciferase reporter assay was performed to verify the binding relationship between miR-625 and the 3′-UTR of SOX4.Results: The results demonstrated that miR-625 is significantly down-regulated in clinical LSCC tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of LSCC patients. Overexpression of miR-625 significantly suppressed the proliferation, migration, invasion, and EMT of LSCC cells. Furthermore, SOX4 was validated as a direct target of miR-625 in LSCC cells, and rescue experiments suggested that restoration of SOX4 blocked the tumor suppressive role of miR-625 in LSCC cells.Conclusions: Taken together, these findings highlighted a critical role of miR-625 in the pathogenesis of LSCC, and restoration of miR-625 could be considered as a potential therapeutic strategy against this fatal disease.

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