Scholarlink

Background <p>Endothelial cell-specific molecule-1 (ESM1) is a secreted protein involved in a variety of tumors. Nevertheless, the role of ESM1 in oral squamous cell carcinoma (OSCC) is still unclear. This study aimed to elucidate the function and mechanisms of ESM1 in OSCC.</p> Methods <p>Differences in ESM1 expression in OSCC and para-carcinoma tissues were detected by immunohistochemistry, and an ESM1 overexpression human umbilical vein endothelial cell (HUVEC) model was constructed. CCK-8, EdU staining, and colony formation assays were employed to evaluate cell proliferation capacity, while Transwell and scratch assays were performed to assess cell invasion and migration capabilities. Quantitative polymerase chain reaction and western blotting assays were used to analyze the changes in endothelial–mesenchymal transition (EndMT) markers, and bioinformatics was conducted to verify the role of the NOTCH1/DLL4 pathway. The effects of ESM1 on the malignant phenotype of tumor cells and epithelial–mesenchymal transition (EMT) were detected by a co-culture model of HUVEC and OSCC cells.</p> Results <p>ESM1 was significantly upregulated in OSCC tissues and correlated with advanced T-stage, N-stage, and low immune score. ESM1 was secreted by endothelial cells, and overexpression of ESM1 enhanced the proliferation, migration, and invasion ability of HUVEC, as well as the activation of EndMT. Mechanistically, ESM1 induced EndMT through activating the NOTCH1/DLL4 pathway. Co-culture experiments showed that overexpression of ESM1 in HUVEC significantly promoted the proliferation, migration, invasion, and EMT processes of OSCC cells.</p> Conclusion <p>ESM1 mediates EndMT in endothelial cells through the NOTCH1/DLL4 pathway and promotes EMT and the malignant phenotype of OSCC cells through paracrine effects, suggesting its potential as a therapeutic target for OSCC.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Endothelial cell-specific molecule-1 induces endothelial–mesenchymal transition and epithelial–mesenchymal transition processes to promote oral squamous cell carcinoma progression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月30日

查看全文
  • Ruoyan Zhang,
  • Yuchen Yang,
  • Jun Wang

摘要

Background

Endothelial cell-specific molecule-1 (ESM1) is a secreted protein involved in a variety of tumors. Nevertheless, the role of ESM1 in oral squamous cell carcinoma (OSCC) is still unclear. This study aimed to elucidate the function and mechanisms of ESM1 in OSCC.

Methods

Differences in ESM1 expression in OSCC and para-carcinoma tissues were detected by immunohistochemistry, and an ESM1 overexpression human umbilical vein endothelial cell (HUVEC) model was constructed. CCK-8, EdU staining, and colony formation assays were employed to evaluate cell proliferation capacity, while Transwell and scratch assays were performed to assess cell invasion and migration capabilities. Quantitative polymerase chain reaction and western blotting assays were used to analyze the changes in endothelial–mesenchymal transition (EndMT) markers, and bioinformatics was conducted to verify the role of the NOTCH1/DLL4 pathway. The effects of ESM1 on the malignant phenotype of tumor cells and epithelial–mesenchymal transition (EMT) were detected by a co-culture model of HUVEC and OSCC cells.

Results

ESM1 was significantly upregulated in OSCC tissues and correlated with advanced T-stage, N-stage, and low immune score. ESM1 was secreted by endothelial cells, and overexpression of ESM1 enhanced the proliferation, migration, and invasion ability of HUVEC, as well as the activation of EndMT. Mechanistically, ESM1 induced EndMT through activating the NOTCH1/DLL4 pathway. Co-culture experiments showed that overexpression of ESM1 in HUVEC significantly promoted the proliferation, migration, invasion, and EMT processes of OSCC cells.

Conclusion

ESM1 mediates EndMT in endothelial cells through the NOTCH1/DLL4 pathway and promotes EMT and the malignant phenotype of OSCC cells through paracrine effects, suggesting its potential as a therapeutic target for OSCC.