ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2020
Targeting Toll-like receptor 4 with CLI-095 (TAK-242) enhances the antimetastatic effect of the estrogen receptor antagonist fulvestrant on non-small cell lung cancer.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- The antitumor effect of tlr4 inhibition in head and neck cancer cell lines.Scientific reports · 2025Article
- The Mechanism of Steroid Hormones in Non-Small Cell Lung Cancer: From Molecular Signaling to Clinical Application.Biomedicines · 2025Review
- Targeting the Toll-like Receptor Signaling Pathway in Lung Cancer: Therapeutic Opportunities and Challenges.Current drug targets · 2025Review
- Targeting toll-like receptors: unveiling potential therapeutic strategies for deep vein thrombosis.Frontiers in immunology · 2025Review
- Toll-like Receptors: Key Players in Squamous Cell Carcinoma Progression.Journal of clinical medicine · 2024Article
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7 authors at 3 institutions in 1 country.
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Abstract
purposeEstrogen plays a critical role in the invasiveness and metastasis of non-small cell lung cancer (NSCLC) through estrogen receptor β (ERβ). However, the antimetastatic effect of the ERβ antagonist fulvestrant was still limited in NSCLC patients. Recently, Toll-like receptor 4 (TLR4) signaling was implicated in NSCLC metastasis. Our present study aimed to evaluate the synergistic antimetastatic effect of a combination of fulvestrant and the TLR4-specific inhibitor CLI-095 (TAK-242) on human NSCLC cells.
methodsThe expression levels of ERβ and TLR4 were detected by immunohistochemical (IHC) analysis of 180 primary NSCLC and 30 corresponding metastatic lymph node samples. The association between ERβ and TLR4 expression was analyzed. The aggressiveness of NSCLC cells treated with fulvestrant, CLI-095 or the drug combination and formation status of their invadopodia, invasion-associated structures, were investigated. The protein levels in NSCLC cells in different groups were determined by Western blot and immunofluorescence analyses.
resultsHere, a positive correlation between ERβ and TLR4 expression was observed in both primary NSCLC tissue (Spearman's Rho correlation coefficient = 0.411, p < 0.001) and metastatic lymph node tissue (Spearman's Rho correlation coefficient = 0.374, p = 0.009). The protein levels of ERβ in NSCLC cell lines were decreased by fulvestrant, and this suppressive effect was significantly enhanced when fulvestrant was combined with CLI-095 (p < 0.05). Both the migration and invasion of NSCLC cells were suppressed by fulvestrant or CLI-095 alone, and the combination of fulvestrant + CLI-095 showed the strongest inhibitory effect (p < 0.05). In addition, the results demonstrated that CLI-095 also helped fulvestrant restrict the formation and function of invadopodia in NSCLC cells (p < 0.05).
conclusionsCollectively, our study results suggested that CLI-095 enhances the antimetastatic effect of fulvestrant on NSCLC and provided support for further investigation of the antitumor activity of combined therapy with antiestrogen and anti-TLR4 agents in the clinic.
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