ArticleJournal of experimental & clinical cancer research : CR2015
CCL21-CCR7 promotes the lymph node metastasis of esophageal squamous cell carcinoma by up-regulating MUC1.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Lymphatic immunomodulation using engineered drug delivery systems for cancer immunotherapy.Advanced drug delivery reviews · 2020Pooled it
- CCL21/CCR7 axis regulates VEGF-D mHuman cell · 2026Article
- SMYD2 regulates lymph node metastasis derived from intrahepatic cholangiocellular carcinoma through CCR7-dependent chemotaxis.Scientific reports · 2026Article
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- Co-expression of CCR7 and H3K9me3 identifies aggressive B-cell lymphoma with bone marrow infiltration and poor prognosis.European cytokine network · 2026Article
- IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.Cancer cell · 2026Article
- Differential expression pattern of CC chemokine receptor 7 guides precision treatment of hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- A novel peptide targeting CCR7 inhibits tumor cell lymph node metastasis.Cancer immunology, immunotherapy : CII · 2025Article
- The multifaceted roles of mucins family in lung cancer: from prognostic biomarkers to promising targets.Frontiers in immunology · 2025Review
- Chemokines and their receptors in the esophageal carcinoma tumor microenvironment: key factors for metastasis and progression.Frontiers in oncology · 2025Review
- Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy.Frontiers in immunology · 2024Review
- EMT-related gene risk model establishment for prognosis and drug treatment efficiency prediction in hepatocellular carcinoma.Scientific reports · 2023Article
- High-fat diet, but not duration of lactation, increases mammary gland lymphatic vessel function and subsequent growth of inflammatory breast cancer cells.Journal of mammary gland biology and neoplasia · 2023Article
- Article
- Mechanisms of esophageal cancer metastasis and treatment progress.Frontiers in immunology · 2023Review
- C-C Chemokine Receptor 7 in Cancer.Cells · 2022Review
- Circulating Tumor Cells: Does Ion Transport Contribute to Intravascular Survival, Adhesion, Extravasation, and Metastatic Organotropism?Reviews of physiology, biochemistry and pharmacology · 2022Review
- Shared network pattern of lung squamous carcinoma and adenocarcinoma illuminates therapeutic targets for non-small cell lung cancer.Frontiers in surgery · 2022Article
- The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma.Frontiers in oncology · 2022Review
- Paclitaxel treatment enhances lymphatic metastasis of B16F10 melanoma cells via CCL21/CCR7 axis.International journal of biological sciences · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCCR7 and MUC1 are correlated with lymph node metastasis in ESCC, but the role of MUC1 in the CCR7-induced lymphatic metastasis and the underlying molecular mechanism is still unclear.
methodsThe expression of CCR7 and MUC1 was detected in the ESCC samples by IHC, and the clinical significance of CCR7 and MUC1 in ESCC was analyzed. The expression of CCR7 and MUC1 in ESCC cell lines was detected by qRT-PCR and western blot. The effect of CCL21 on the migration and invasion of ESCC cells was determined by transwell assay. The activity of MUC1 promoter was determined by luciferase reporter assay. The activation of Erk, Akt and Sp1 was detected by western blot and the binding of Sp1 to the MUC1 promoter was determined by ChIP.
resultsThe co-expression of CCR7 and MUC1 was detected in 153 ESCC samples by IHC, and both were correlated with lymph node metastasis, regional lymphatic recurrence and poor prognosis. Correspondingly, increasing levels of MUC1 mRNA and protein were detected in the ESCC cell lines KYSE410 and Eca9706 after treatment with CCL21 in a time- and dose-dependent manner. Furthermore, silencing MUC1 could remarkably suppress the invasion and migration of ESCC cells induced by CCL21. Moreover, heterologous CCR7 promoted the invasion and migration of KYSE150 and up-regulated MUC1 expression. Increasing levels of activated ERK1/2 and Akt were detected in KYSE410 after treating the cells with CCL21, and inhibiting the activation of ERK1/2 but not Akt caused the increased transcription of MUC1. Finally, the phosphorylation of Sp1 induced by ERK1/2 and subsequent increases in the binding of Sp1 to the muc1 promoter at -99/-90 were confirmed to cause the up-regulation of MUC1 induced by CCL21-CCR7.
conclusionsOur findings suggested that MUC1 plays an important role in CCL21-CCR7-induced lymphatic metastasis and may serve as a therapeutic target in ESCC.
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