EGR1 IS NEGATIVELY ASSOCIATED WITH HNSCC CELL INVASION VIA INHIBITION OF MMP9 AND MDM2

Abstract

Objectives The effect of early growth response-1 (EGR1) on cancer invasion remains controversial depending on the cancer type. EGR1 is known to slow the progression of cancer by inhibiting the expression of MMP2. However, the effect of EGR1 on MMP9, which is important for HNSCC invasion, is disputed. Our aim is to clarify the tumor suppressor role of EGR1 in downregulating MMP9. We also consider MDM2, an enhancer of MMP9 expression. Findings EGR1 mRNA and protein expression were compared in normal and HNSCC tissues using The Cancer Genome Atlas (TCGA) dataset analysis as well as immunohistochemistry (IHC). In vitro cell invasion was performed by two-dimension (2-D) and three-dimension (3-D) spheroids Matrigel invasion assay. TCGA data showed significantly higher EGR1 mRNA levels in nonmetastatic HNSCC tissues than in metastatic tissues. IHC analysis showed significantly higher levels of nuclear EGR1 expression in primary tumor tissues than in paired metastatic lymph node tissues. Transient EGR1 overexpression inhibited the Matrigel invasion of HNSCC cells, as well as decreasing mRNA of MMP9 and MDM2. Consistent with these observations, TCGA data analysis found significantly fewer metastatic patients among a subgroup of a large population presenting higher EGR1 expressions with lower MMP9 and/or MDM2. Conclusions Our data suggests that EGR1 might be a potential candidate to attenuate HNSCC metastasis.