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Activating transcription factor 1 (ATF1) overexpression correlates with tumor progression in multiple tumors, and yet the involvement of ATF1 in gastrointestinal cancer development and progression remains unclear.In this study,we investigated the clinical significance and biological effects ofATF 1 in esophageal squamous cellcarcinoma (ESCC).Immunohistochemical studies revealed a high prevalence of active ATF 1 overexpression (58.8%), which was significantly associated with lymph node metastasis (P =0.01 1).Lentivirus-mediated shRNA stably inhibited ATF 1 protein expression in ESCC cell lines.In addition, inhibition the expression of ATF1 significantly reduced cell invasion and motility and enhanced the apoptosis in ESCC cell lines in vitro.Moreover, lentiverus-mediated shRNA targeting ATF1 enhances chemosensitivity of esophageal squamous cell carcinoma cells to cisplatin.Taken together, these findings suggest that ATF 1 overexpression promotes cell motility and lymph node metastasis in ESCC and ATF1 constitutes a potential biomarker and therapeutic target in ESCCs with lymph node metastases.