Dataset Information

MMP14 regulates cell migration and invasion through epithelial-mesenchymal transition in nasopharyngeal carcinoma.

ABSTRACT: Matrix metalloproteinase 14 (MMP14) has been shown to play a significant role in several types of cancers, but little is known about the function of MMP14 in nasopharyngeal carcinoma (NPC) carcinogenesis. The aim of this study was to investigate the role of MMP14 in NPC using NPC tumor samples or tissue microarray. We have shown that MMP14 was increased in NPC samples compared with normal nasopharynx (NP) tissues in microarray data (GSE13597). Both MMP14 mRNA and protein expression were markedly higher in NPC tissues than in NP tissues. High levels of MMP14 protein were found positively correlate with the status of late clinical stages of tumor and tumor with lymph node metastasis. Moreover, we have shown that MMP14 expression promoted the cell migration and invasion of NPC cells in vitro and regulated the expression of EMT-associated genes. Our data demonstrated that MMP14 plays an important role in regulation of migration and invasion of NPC cells, and constitutes a potential novel therapeutic target for NPC.

SUBMITTER: Yan T

PROVIDER: S-EPMC4494146 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MMP14 regulates cell migration and invasion through epithelial-mesenchymal transition in nasopharyngeal carcinoma.

Yan Tinghua T Lin Zhonghao Z Jiang Jinhua J Lu Suiwan S Chen Miaoan M Que Huaxing H He Xiangsheng X Que Ganbo G Mao Jianfeng J Xiao Jinan J Zheng Qingwei Q

American journal of translational research 20150515 5

Matrix metalloproteinase 14 (MMP14) has been shown to play a significant role in several types of cancers, but little is known about the function of MMP14 in nasopharyngeal carcinoma (NPC) carcinogenesis. The aim of this study was to investigate the role of MMP14 in NPC using NPC tumor samples or tissue microarray. We have shown that MMP14 was increased in NPC samples compared with normal nasopharynx (NP) tissues in microarray data (GSE13597). Both MMP14 mRNA and protein expression were markedly ...[more]

PMID: 26175856

Similar Datasets

Project description:PurposeThe aim of this work was to investigate the clinicopathological significance of fibrinogen gamma chain (FGG) and its biological roles during hepatocellular carcinoma (HCC) development and progression.MethodsThe expression of FGG was examined by Western blot and reverse transcription quantitative PCR in two different sample sets, including 24 or 35 pairs of HCC tumor tissues and their corresponding adjacent non-tumorous tissues. Afterward, association analysis between the expression of FGG and clinicopathological characteristics was systematically analyzed in 79 HCC patients. Subsequently, the mobility and invasiveness of SK-HEP-1 cells with FGG overexpression or knockdown were evaluated by transwell assay and wound healing assay. Additionally, the expressions of epithelial to mesenchymal transition (EMT)-associated markers were also detected in FGG overexpressed or silenced SK-HEP-1 cells.ResultsThe expression of FGG was significantly increased in primary HCC tissues comparing with its corresponding adjacent non-tumorous tissues. Clinical pathological analysis demonstrated that upregulation of intracellular FGG was significantly associated with increased vascular invasion, more satellite nodules, and more advanced TNM stage, and HCC patients with stronger expression of FGG had a higher recurrence rate and correspondingly a shorter overall survival time. Meanwhile, the high expression of FGG was also proved to be an independent risk factor for disease-free survival after surgical resection. In vitro phenotype studies showed that overexpression of FGG could promote the migration and invasion in SK-HEP-1 cells; conversely, these phenotypes could be significantly inhibited by knocking down the expression of FGG. Mechanism studies indicated that FGG could promote the migration and invasion through EMT signaling pathway by regulating the expressions of Slug and ZEB1.ConclusionFGG played important roles in enhancing cancer cell motility and invasiveness through EMT signaling, and might serve as a potential prognostic biomarker for HCC patients.

Project description:BackgroundTo examine whether MLKL participated in the invasion of radiosensitive nasopharyngeal carcinoma (NPC) cell (CNE-2) and radioresistant NPC cell (CR) through regulating epithelial-mesenchymal transition (EMT).MethodssiRNA and CRISPR/Cas9 technique were used to decrease MLKL expression in NPC cell (CNE-2 and CR). Trans-well assay was conducted to evaluate invasion. Gene expression profiling was performed using Human U133 2.0 plus arrays (Affymetrix). Kyoto Encyclopedia of Genes and Genomes (KEGG) was adopted to analyze gene expression profiling. Hub genes at a functional level were accessed by protein-to-protein network (PPI). Quantitative real-time PCR and Western blot were used to access EMT markers.ResultsInvasion of CR was about 3~fold change higher than that of CNE-2. Silencing MLKL by siRNA inhibited invasion of CR, not CNE-2. Further, depleting MLKL by CRISPR-Cas9 in CR (CR-MLKL KO) also inhibited its invasion. KEGG pathway analysis showed invasion-related pathways were altered, such as adherent junction, TGF-β signaling pathway. PPI demonstrated that compared with CNE-2, CR showed 9 elevated hub genes including EGFR, JUN, CD44, SPP1, VIM, IL-8, BCL2, WDFY2, PIK3CD and 1 downregulated hub gene CDH1. After MLKL depletion, 8 hub genes were downregulated (EGFR, JUN, CD44, SPP1, VIM, FGF13, PLAU, MMP1) and 2 hub genes were upregulated (MMP9, CDH1). Quantitative real-time PCR results showed that compared with CNE-2, CR displayed decreased epithelial markers significantly (E-Cadherin) and increased mesenchymal markers significantly (Vimentin, N-Cadherin, Zeb1), indicating irradiation-induced EMT. After depletion of MLKL in CR, the expression of E-Cadherin, Vimentin, N-Cadherin, Zeb1 was reversed to the level of CNE-2. Western blot confirmed the results from qRT-PCR.ConclusionsDepletion of MLKL efficiently inhibits invasion of radioresistant NPC by suppressing EMT. MLKL may be an important target to suppress distant metastasis of NPC patients who relapsed after radiotherapy.

Dataset Information

MMP14 regulates cell migration and invasion through epithelial-mesenchymal transition in nasopharyngeal carcinoma.

Publications

MMP14 regulates cell migration and invasion through epithelial-mesenchymal transition in nasopharyngeal carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets