SERPINE2 promotes esophageal squamous cell carcinoma metastasis by activating BMP4.

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.

Zhang J ，Luo A ，Huang F ，Gong T ，Liu Z ... -  《-》

[SERPINE2 promotes cellular migration and invasion in esophageal squamous cell carcinoma by activating β-catenin].

Zhang JL ，Luo AP ，Huang FR ，Gong TY ，Liu ZH ... -  《-》

HERG1 promotes esophageal squamous cell carcinoma growth and metastasis through TXNDC5 by activating the PI3K/AKT pathway.

Wang H ，Yang X ，Guo Y ，Shui L ，Li S ，Bai Y ，Liu Y ，Zeng M ，Xia J ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

LHX2 Enhances the Malignant Phenotype of Esophageal Squamous Cell Carcinoma by Upregulating the Expression of SERPINE2.

Li X ，Wu X ，Chen H ，Liu Z ，He H ，Wang L ... -  《-》

BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial-mesenchymal transition and angiogenesis.

Metastasis to regional lymph nodes or distal organs predicts the progression of the disease and poor prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies demonstrated that BTB and CNC homology 1 (BACH1) participates in various types of tumor metastasis. However, the function of BACH1 in ESCC was rarely reported. The present study demonstrated that BACH1 protein was overexpressed in ESCC tissues compared with paired esophageal epithelial tissues according to immunohistochemical staining (IHC). Higher levels of BACH1 mRNA were associated with decreased overall survival (OS) and shorter disease-free survival (DFS) of ESCC patients based on an analysis of The Cancer Genome Atlas (TCGA) datasets. BACH1 significantly enhanced the migration and invasion of ESCC in vitro. Mechanistically, BACH1 promoted the epithelial-mesenchymal transition (EMT) by directly activating the transcription of CDH2, SNAI2, and VIM, as determined by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). BACH1 overexpression significantly enhanced CDH2 promoter activity according to the results of a luciferase assay. The results of subsequent experiments indicated that BACH1 enhanced the growth of tumor xenografts. The density of CD31+ blood vessels and the expression of vascular endothelial growth factor C (VEGFC) in tumor xenografts were significantly associated with BACH1 levels according to the results of IHC and immunofluorescence (IF) analyses performed in vivo. Moreover, ChIP-qPCR analysis demonstrated that the transcriptional activity of VEGFC was also upregulated by BACH1. Thus, BACH1 contributes to ESCC metastasis and tumorigenesis by partially facilitating the EMT and angiogenesis, and BACH1 may be a promising therapeutic target or molecular marker in ESCC.

Zhao Y ，Gao J ，Xie X ，Nan P ，Liu F ，Sun Y ，Zhao X ... -  《Cancer Medicine》