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<p>Distant metastasis remains the primary cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, it is essential to explore the regulatory mechanisms underlying NPC metastasis. Ets variant 5 (ETV5) is a transcription factor demonstrated to be overexpressed in various malignancies. However, the function of ETV5 in NPC is poorly characterized. We aim to investigate the function and mechanisms of ETV5 in NPC development. We assessed ETV5 expression in nasopharyngeal carcinoma tissues from 99 patients using quantitative immunohistochemistry. ETV5 levels in the cell lines 6-10B, CNE2, 5-8F, and S18 were determined using Western blotting. Cell proliferation, migration, and invasion capabilities were assessed using colony formation, scratch, and Transwell assays. The binding of ETV5 to promoter of leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) was detected by dual luciferase reporter gene detection system. We found that ETV5 overexpression was significantly correlated with poorer prognosis in NPC patients. Based on endogenous ETV5 expression, ETV5 overexpressing and downregulation cell lines were established. Functional analyses were conducted using CCK-8, colony formation, wound healing, and transwell assays. Elevated ETV5 expression promotes NPC cell proliferation and invasion migration, while knocking down ETV5 has the opposite effect. Mechanistically, ETV5 transcriptionally activates of LGR4 by directly binding to its promoter region. Our study revealed that ETV5 induces cell proliferation, invasion and migration by upregulating LGR4 in NPC. ETV5/LGR4 signaling may serve as a therapeutic target for NPC patients.</p>

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ETV5 transcriptionally activates LGR4 and promotes cancer cell invasion and migration of nasopharyngeal carcinoma

  • 期刊论文

  • 发表日期：

    2025年10月29日

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  • Lei Zeng,
  • QiWei Luo,
  • Nan Liu,
  • AoChen Shi,
  • LuLu Liu,
  • Lei Tao,
  • KaiBin Zhu,
  • Yan Liu,
  • XianMing He,
  • JianZe Zhang,
  • ZeQun Huang,
  • Su Deng,
  • JiaYin Wu,
  • Ping Zhang,
  • Yi Sang

摘要

Distant metastasis remains the primary cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, it is essential to explore the regulatory mechanisms underlying NPC metastasis. Ets variant 5 (ETV5) is a transcription factor demonstrated to be overexpressed in various malignancies. However, the function of ETV5 in NPC is poorly characterized. We aim to investigate the function and mechanisms of ETV5 in NPC development. We assessed ETV5 expression in nasopharyngeal carcinoma tissues from 99 patients using quantitative immunohistochemistry. ETV5 levels in the cell lines 6-10B, CNE2, 5-8F, and S18 were determined using Western blotting. Cell proliferation, migration, and invasion capabilities were assessed using colony formation, scratch, and Transwell assays. The binding of ETV5 to promoter of leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) was detected by dual luciferase reporter gene detection system. We found that ETV5 overexpression was significantly correlated with poorer prognosis in NPC patients. Based on endogenous ETV5 expression, ETV5 overexpressing and downregulation cell lines were established. Functional analyses were conducted using CCK-8, colony formation, wound healing, and transwell assays. Elevated ETV5 expression promotes NPC cell proliferation and invasion migration, while knocking down ETV5 has the opposite effect. Mechanistically, ETV5 transcriptionally activates of LGR4 by directly binding to its promoter region. Our study revealed that ETV5 induces cell proliferation, invasion and migration by upregulating LGR4 in NPC. ETV5/LGR4 signaling may serve as a therapeutic target for NPC patients.