ArticleStem cell research & therapy2022
Epiregulin increases stemness-associated genes expression and promotes chemoresistance of non-small cell lung cancer via ERK signaling.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Association of CYP24A1 with survival and drug resistance in clinical cancer patients: a meta-analysis.BMC cancer · 2022Pooled it
- Suppression of LTBP1 enhances the sensitivity of bladder cancer to cisplatin.Scientific reports · 2026Article
- EREG promotes colorectal cancer progression and immune suppressive microenvironment formation through IL-17A/NF-κB pathway.Discover oncology · 2026Article
- MicroRNA-Mediated Regulation of Cancer Stem Cells: Implications for Radioresistance and Chemoresistance in Cancer Treatment.MicroRNA (Shariqah, United Arab Emirates) · 2026Review
- ST6GAL1 promotes cancer stem-like cell-associated paclitaxel resistance through the EGFR-mTOR-SOX2/BMI1 axis in non-small cell lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- To develop prognostic markers related to drug resistance in pancreatic cancer patients based on multiple machine learning methods.Annals of medicine and surgery (2012) · 2025Article
- Transcriptomic Signatures in TP53 Positive and Negative Tumor Samples in NSCLC.Current gene therapy · 2025Article
- TRIM19 enhances the chemosensitivity of endometrial cancer by regulating the TBX2/NRF2 axis.Discover oncology · 2025Article
- Role of epiregulin levels in polycystic ovary syndrome patients: new findings and clinical significance.Revista da Associacao Medica Brasileira (1992) · 2025Article
- Inhibition of EREG/ErbB/ERK by Astragaloside IV reversed taxol-resistance of non-small cell lung cancer through attenuation of stemness via TGFβ and Hedgehog signal pathway.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Integrative ensemble modelling of cetuximab sensitivity in colorectal cancer patient-derived xenografts.Nature communications · 2024Article
- Alterations in miRNA Expression and Their Role in the Pathogenesis of Cervical Cancer.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Review
- Long noncoding RNA NONHSAT160169.1 promotes resistance via hsa-let-7c-3p/SOX2 axis in gastric cancer.Scientific reports · 2023Article
- Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin-Induced Resistance and Stemness in Human Lung Cancer A549 Cells.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Integrative bioinformatics approaches to establish potential prognostic immune-related genes signature and drugs in the non-small cell lung cancer microenvironment.Frontiers in pharmacology · 2023Article
- Value of plasma vitamin D level and nomogram model for predicting the prognosis of patients with small cell lung cancer treated with platinum plus etoposide as first-line chemotherapy.American journal of translational research · 2022Article
- WDR72 Enhances the Stemness of Lung Cancer Cells by Activating the AKT/HIF-1Journal of oncology · 2022Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemoresistance often causes the failure of treatment and death of patients with advanced non-small-cell lung cancer. However, there is still no resistance genes signature and available enriched signaling derived from a comprehensive RNA-Seq data analysis of lung cancer patients that could act as a therapeutic target to re-sensitize the acquired resistant cancer cells to chemo-drugs. Hence, in this study, we aimed to identify the resistance signature for clinical lung cancer patients and explore the regulatory mechanism.
methodAnalysis of RNA-Seq data from clinical lung cancer patients was conducted in R studio to identify the resistance signature. The resistance signature was validated by survival time of lung cancer patients and qPCR in chemo-resistant cells. Cytokine application, small-interfering RNA and pharmacological inhibition approaches were applied to characterize the function and molecular mechanism of EREG and downstream signaling in chemoresistance regulation via stemness.
resultsThe RTK and vitamin D signaling were enriched among resistance genes, where 6 genes were validated as resistance signature and associated with poor survival in patients. EREG/ERK signaling was activated by chemo-drugs in NSCLC cells. EREG protein promoted the NSCLC resistance to chemo-drugs by increasing stemness genes expression. Additionally, inhibition of EREG/ErbB had downregulated ERK signaling, resulting in decreased expression of stemness-associated genes and subsequently re-sensitized the resistant NSCLC cells and spheres to chemo-drugs.
conclusionsThese findings revealed 6 resistance genes signature and proved that EREG/ErbB regulated the stemness to maintain chemoresistance of NSCLC via ERK signaling. Therefore, targeting EREG/ErbB might significantly and effectively resolve the chemoresistance issue.
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