CCAAT/Enhancer Binding Protein β-Mediated MMP3 Upregulation Promotes Esophageal Squamous Cell Cancer Invasion In Vitro and Is Associated with Metastasis in Human Patients.

Aims: Metastasis is a significant obstacle to curing esophageal squamous cell carcinoma (ESCC). The CCAAT/enhancer binding protein β (C/EBPβ) and matrix metalloproteinase 3 (MMP3) are thought to play key roles in cancer invasion and metastasis. In this study, we aimed to detect whether C/EBPβ-mediated tumor invasion was dependent on MMP3. In addition, we determined whether C/EBPβ upregulation was associated with MMP3 levels and metastatic status in patients with ESCC. Materials and Methods: A total of 126 patients with ESCC were recruited for this study. The mRNA and protein levels of C/EBPβ and MMP3 in ESCC cell lines and specimens from ESCC patient were determined by reverse transcription-polymerase chain reaction and western blot, respectively. Tumor cell invasion was analyzed using an in vitro Matrigel Invasion Assay. The correlation between C/EBPβ and MMP3 expression was determined by Pearson's correlation analysis. Results: Both mRNA and protein levels of MMP3 were upregulated by C/EBPβ overexpression and downregulated by C/EBPβ siRNA in KYSE150 cell cultures. The promotion of ESCC cell invasion through C/EBPβ was inhibited by MMP3 siRNA. The level of C/EBPβ was correlated with MMP3 and metastatic status in patients with ESCC. Conclusions: C/EBPβ upregulation promoted tumor cell invasion in an MMP3-dependent manner in vitro and was associated with metastatic status in ESCC.