SUMO modified ETV1 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by facilitating CCL2 transcription in esophageal squamous cell carcinoma cells

作者：Tianci Han, Xiaoqi Guo, Junwei Xie, Tong Wei, Liang Zhang · 发表于：Cancer Immunology Immunotherapy · 年份：2025 · DOI：10.1007/s00262-024-03914-z · 被引用次数：10 · 研究领域：Immune cells in cancer、Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a high metastasis rate and a poor prognosis. ETS variant transcription factor 1 (ETV1) plays an important role in multiple malignancies. However, its function in ESCC progression and tumor microenvironment (TME) remains to be explored. In this study, we characterized the role of ETV1 in ESCC process and TME. METHODS: Gene expression and immune infiltration in ESCC samples from the Cancer Genome Atlas (TCGA) were analyzed. The expression of ETV1 in clinical samples was detected by real-time PCR, western blot and immunohistochemistry staining. Cell growth was detected by CCK-8 and colony formation assays. Macrophage phenotypes were determined using flow cytometry. Immunofluorescence double staining was used to detect the tumor-associated macrophage (TAM) infiltration. The tumor volume was recorded and weighed. Transcriptional activity was measured using dual-luciferase assay, chromatin immunoprecipitation (ChIP) assay and DNA pull-down assay. RESULTS: In this study, through analysis of ESCC samples from TCGA database and the clinic, we noticed that ETV1 was highly expressed in ESCC tumor tissues and was associated with TAM infiltration. Overexpression of ETV1 promoted ESCC cell proliferation in vitro and xenograft tumor growth in nude mice, while ETV1 knockdown elicited the opposite effects. Furthermore, ETV1 upregulation in tumor tissues was found to drive M2 macrophage infiltr...