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.