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

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...

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Bibliographic Details
Published in:Cancers 2019-03, Vol.11 (3), p.315
Main Authors: Kim, Jinkyung, Kang, Sung-Min, Oh, Su Young, Lee, Heon-Jin, Lee, Inhan, Hwang, Jae-Chan, Hong, Su-Hyung
Format: Article
Language:English
Subjects:
Binding sites
Cancer
Cell growth
Chromatin
EGR-1 protein
Epidermal growth factor
Gelatinase A
Gelatinase B
Genomes
Head & neck cancer
Human papillomavirus
Immunoprecipitation
Kinases
Medical prognosis
Metastases
Metastasis
Protein expression
Proteins
Sp1 protein
Squamous cell carcinoma
Transcription activation
Transcription factors
Tumors
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Summary: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 and was evaluated by chromatin immunoprecipitation (ChIP) and promoter luciferase assay. The correlation between - 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 and 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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11030315