Interaction of estrogen receptor β5 and interleukin 6 receptor in the progression of non–small cell lung cancer

Tang, Huiping; Bai, Yuquan; Xiong, Lei; Zhang, Li; Wei, Yanhong; Zhu, Minghua; Wu, Xiaoling; Ding, Long; Yang, Junhui; Yu, Li; Xu, Shuai; Zhao, Jinping

doi:10.1002/jcb.27510

Cited by 8 publications

(5 citation statements)

References 30 publications

(71 reference statements)

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“…Several studies have shown that the estrogen receptor beta (ESR2) appeared in many tumors, including lung cancer, wherein ESR2 and interleukin 6 receptor (IL-6R) interacts to mediate lung cancer progression. Cell proliferation, invasion, and cell cycle were significantly increased, and cell apoptosis was markedly inhibited by the concurrent action of ESR2 and IL-6 in A549 cells [ 34 ]. Chen et al [ 35 ] showed that phosphorylated ESR1 could directly bind to the promoter of FOSL1 (FOS-like 1) in ESCs/DSCs.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Analysis of the Effects of Corydalis decumbens (Thunb.) Pers. in Non-Small Cell Lung Cancer

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Non-small cell lung cancer (NSCLC) is one of the most malignant tumors worldwide. The main treatment for NSCLC is based on Western medicine; however, the overall effect is unsatisfactory. This study aimed to investigate the potential therapeutic targets and pharmacological mechanisms of action of the traditional Chinese medicine Corydalis decumbens (Thunb.) Pers. in NSCLC based on network pharmacology and bioinformatics. The overlapping genes between Corydalis decumbens (Thunb.) Pers. and NSCLCs were screened using Venn analysis. Cytoscape 3.7.1 software was used to analyze the overlapping target protein-protein interaction (PPI) network. Gene ontology and pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomics database were performed to exploring biological functions of the overlapping genes. The gene expression profiling interactive analysis dataset was used to analyze the correlation between hub gene expression and disease. This study revealed 38 nodes with 191 edges, which may be therapeutic targets for NSCLC. PPI network analysis showed that the most likely association was between the genes AR and NCOA2, NCOA2, and RXRA and ESR1 and NCOA2. These overlapping genes were mainly enriched in the estrogen signaling pathway, calcium signaling pathway, cholinergic synapse, and PI3K-Akt signaling pathway. ESR2 mRNA levels were signiﬁcantly downregulated in patients with lung adenocarcinoma (LUAD) getting worse, and KDR levels were lower in lung squamous cell carcinoma (LUSC) than those in normal tissue. PTGS2 expression was correlated with the median survival time of LUAD, and ESR1 expression was correlated with the median survival time of LUSC. The application of network pharmacology revealed the potential mechanism underlying the effects of Corydalis decumbens (Thunb.) Pers. in NSCLC treatment and provided a theoretical basis for further in-depth research in this field.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Analysis of the Effects of Corydalis decumbens (Thunb.) Pers. in Non-Small Cell Lung Cancer

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Therefore, assessing the function of ERb splice variants other than ERb1 is equally important. Notably, the crucial role of ERb5 in lung cancer is becoming increasingly evident (17,24). In this study, we focused on the role of ERb1 and ERb5 in lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Receptor β1 Expression Patterns Have Different Effects on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors’ Treatment Response in Epidermal Growth Factor Receptor Mutant Lung Adenocarcinoma

et al. 2021

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Estrogen receptor β (ERβ) can regulate cellular signaling through non-genomic mechanisms, potentially promoting resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanisms underlying the ERβ-mediated resistance to EGFR TKIs remain poorly understood. In this study, we investigated the role of the interaction between ERβ1 and ERβ5 in non-genomic signaling in lung adenocarcinoma. We established PC9 cell lines stably overexpressing ERβ1 or ERβ1/ERβ5. Immunofluorescence revealed that ERβ5 overexpression partly retained ERβ1 in the cytoplasm. Immunoblotting analyses revealed that EGFR pathway activation levels were higher in PC9/ERβ1/5 cells than those in PC9/ERβ1 or control PC9 cells. In the presence of estradiol, PI3K/AKT/mTOR pathway activation levels were higher in ERβ1/5-expressing cells than those in ERβ1-expressing cells. Additionally, PC9/ERβ1/5 cells were less prone to the cytotoxic and pro-apoptotic effects of gefitinib compared with PC9/ERβ1 or control PC9 cells. Cytoplasmic ERβ1 was associated with poor progression-free survival in lung cancer patients treated with EGFR TKIs. These results suggest that cytoplasmic ERβ1 was responsible for EGFR TKI resistance slightly through non-genomic mechanism in EGFR mutant lung adenocarcinoma.

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“…Therefore, assessing the function of ERβ splice variants other than ERβ1 is equally important. Notably, the crucial role of ERβ5 in lung cancer is becoming increasingly evident [17,24].…”

Section: Discussionmentioning

confidence: 99%

ERβ1 Expression Patterns Have Different Effects On EGFR TKIs Treatment Response in EGFR Mutant Lung Adenocarcinomas.

Zhang

Tian

Lin

et al. 2020

Preprint

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Background: Estrogen receptor β (ERβ) can regulate cellular signaling through non-genomic mechanisms, potentially promoting resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanisms underlying the ERβ-mediated resistance to EGFR TKIs remain poorly understood. Methods: qRT-PCR was performed to investigate ERβ1 and ERβ5 expression levels in cell lines. The localization of ERβ and ERβ1 within cells was assessed using immunocytochemistry and immunofluorescence. The effect of estradiol and/or gefitinib on EGFR signaling pathways was determined by western blot. Cell viability and colony formation assays were used to assess gefitinib response for different cell lines. The apoptosis was verified by tunel and western blot. Immunohistochemistry was used to assess the expression of ERβ1 in lung adenocarcinoma tissues. Patient survival was estimated using the Kaplan-Meier method, and comparisons between groups were conducted using log-rank tests. Results: PC9 cell lines stably overexpressing ERβ1 or ERβ1/ERβ5 were established successfully. Immunofluorescence revealed that ERβ5 overexpression partly retained ERβ1 in the cytoplasm. Immunoblotting analyses revealed that EGFR pathway activation levels were higher in PC9/ERβ1/5 cells than those in PC9/ERβ1 or control PC9 cells. In the presence of estradiol, PI3K/AKT/mTOR pathway activation levels were higher in ERβ1/5-expressing cells than those in ERβ1-expressing cells. Additionally, PC9/ERβ1/5 cells were less prone to the cytotoxic and pro-apoptotic effects of gefitinib compared with PC9/ERβ1 or control PC9 cells. Conclusion: Cytoplasmic ERβ1 was associated with poor progression-free survival in lung cancer patients treated with EGFR TKIs. These results suggest that anti-estrogen therapy might reverse EGFR TKI treatment resistance to some extent in selected patients.

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Interaction of estrogen receptor β5 and interleukin 6 receptor in the progression of non–small cell lung cancer

Cited by 8 publications

References 30 publications

Network Pharmacology-Based Analysis of the Effects of Corydalis decumbens (Thunb.) Pers. in Non-Small Cell Lung Cancer

Network Pharmacology-Based Analysis of the Effects of Corydalis decumbens (Thunb.) Pers. in Non-Small Cell Lung Cancer

Estrogen Receptor β1 Expression Patterns Have Different Effects on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors’ Treatment Response in Epidermal Growth Factor Receptor Mutant Lung Adenocarcinoma

ERβ1 Expression Patterns Have Different Effects On EGFR TKIs Treatment Response in EGFR Mutant Lung Adenocarcinomas.

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