1. Academic Validation
  2. SERPINE2 promotes esophageal squamous cell carcinoma metastasis by activating BMP4

SERPINE2 promotes esophageal squamous cell carcinoma metastasis by activating BMP4

  • Cancer Lett. 2020 Jan 28;469:390-398. doi: 10.1016/j.canlet.2019.11.011.
Jianglan Zhang 1 Aiping Luo 1 Furong Huang 1 Tongyang Gong 1 Zhihua Liu 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 2 State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: liuzh@cicams.ac.cn.
Abstract

Metastasis is a major lethal cause of esophageal squamous cell carcinoma (ESCC) and confers a poor prognosis. Previous studies demonstrated that serpin family E member 2 (SERPINE2) is involved in tumor metastasis. However, the function and mechanism of SERPINE2 in ESCC metastasis remains unclear. In this study, we found that SERPINE2 was increased in ESCC and associated with tumor metastasis. SERPINE2 knockdown inhibited tumor cell invasion and lymph node and lung metastasis by inducing epithelial-mesenchymal transition (EMT). We identified a total of 410 differentially expressed genes in SERPINE2-knockdown cells by RNA-Seq analysis. Among them, bone morphogenetic protein 4 (BMP4) was significantly downregulated. Conversely, BMP4 was increased in SERPINE2-overexpressing cells. Inhibiting BMP4 could attenuate SERPINE2-induced migration and invasion. Moreover, SERPINE2 was positively correlated with clinical stage, tumor invasion depth and lymph node metastasis in ESCC patients. These findings suggest that SERPINE2 promotes tumor metastasis by activating BMP4 and could serve as a potential therapeutic target for clinical intervention in ESCC.

Keywords

BMP4; EMT; ESCC; Metastasis; SERPINE2.

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