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NGFI-A Binding Protein 2 Promotes EGF-Dependent HNSCC Cell Invasion.

Cancers | 2019

NGFI-A binding protein 2 (NAB2) represses the transcriptional activation of early growth response protein-1 (EGR1), a tumor-suppressor. However, Epidermal Growth Factor (EGF) promotes tumor progression even with significant EGR1 upregulation. The molecular mechanism through which NAB2 is involved in cancer is largely unknown. Therefore, we evaluated how the NAB2-mediated suppression of EGR1 facilitates head and neck squamous cell carcinoma (HNSCC) cancer progression, in association with Sp1, which competes with EGR1 as a transcriptional regulator. The effect of NAB2 on EGR1/SP1 binding to the consensus promoter sequences of MMP2 and MMP9 was evaluated by chromatin immunoprecipitation (ChIP) and promoter luciferase assay. The correlation between EGR1-NAB2 expression and metastatic status was investigated using The Cancer Genome Atlas (TCGA) for HNSCC patients. Our data showed that NAB2 knockdown in FaDu and YD-10B HNSCC cells alleviated EGF-dependent increase of Matrigel invasion. In addition, NAB2 upregulation in EGF-treated FaDu cell diminishes EGR1 transcriptional activity, resulting in the upregulation of Sp1-dependent tumor-promoting genes. TCGA data analysis of 483 HNSCC tumors showed that higher levels of both EGR1 and NAB2 mRNA were significantly associated with metastasis, corresponding to in vitro results. Our data suggest that NAB2 upregulation facilitates EGF-mediated cancer cell invasion through the transactivation of Sp1-dependent tumor-promoting genes. These results provide insight into the paradoxical roles of EGF-EGR1 in cancer progression.

Pubmed ID: 30845713 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


β-Actin Antibody (C4) (antibody)

RRID:AB_2714189

This monoclonal targets β-Actin

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MMP-9 (antibody)

RRID:AB_1267245

This monoclonal targets Mmp9

View all literature mentions

Sp1 (PEP 2) (antibody)

RRID:AB_2171050

This polyclonal targets SP1

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E-Cadherin (antibody)

RRID:AB_562059

This monoclonal targets E-Cadherin

View all literature mentions

EGR1 (44D5) Rabbit mAb (antibody)

RRID:AB_2097035

This monoclonal targets EGR1

View all literature mentions

NAB2 (H-180) (antibody)

RRID:AB_2298032

This polyclonal targets NAB2

View all literature mentions

MMP2 antibody [MMP2/8B4] (antibody)

RRID:AB_2145819

This monoclonal targets MMP2

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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Origin (software resource)

RRID:SCR_014212

Software application for data analysis and graphing. Origin contains a variety of different graph types, including statistical plots, 2D and 3D vector graphs, and counter graphs. More advance version is OriginPro which offers advanced analysis tools and Apps for Peak Fitting, Surface Fitting, Statistics and Signal Processing.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions

FaDu (cell line)

RRID:CVCL_1218

Cell line FaDu is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

YD-10B (cell line)

RRID:CVCL_8929

Cell line YD-10B is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

Origin (software resource)

RRID:SCR_014212

Software application for data analysis and graphing. Origin contains a variety of different graph types, including statistical plots, 2D and 3D vector graphs, and counter graphs. More advance version is OriginPro which offers advanced analysis tools and Apps for Peak Fitting, Surface Fitting, Statistics and Signal Processing.

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

View all literature mentions

β-Actin Antibody (C4) (antibody)

RRID:AB_2714189

This monoclonal targets β-Actin

View all literature mentions

NAB2 (H-180) (antibody)

RRID:AB_2298032

This polyclonal targets NAB2

View all literature mentions

MMP2 antibody [MMP2/8B4] (antibody)

RRID:AB_2145819

This monoclonal targets MMP2

View all literature mentions

EGR1 (44D5) Rabbit mAb (antibody)

RRID:AB_2097035

This monoclonal targets EGR1

View all literature mentions

E-Cadherin (antibody)

RRID:AB_562059

This monoclonal targets E-Cadherin

View all literature mentions

FaDu (cell line)

RRID:CVCL_1218

Cell line FaDu is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

MMP-9 (antibody)

RRID:AB_1267245

This monoclonal targets Mmp9

View all literature mentions

Sp1 (PEP 2) (antibody)

RRID:AB_2171050

This polyclonal targets SP1

View all literature mentions

YD-10B (cell line)

RRID:CVCL_8929

Cell line YD-10B is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions