2024/09/10 by Feng-Mei Zhou, Kun‐Kun Wang, Lihong Wang +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Biology #Cancer #Cancer research #Cholangiocarcinoma and Gallbladder Cancer Studies #Epidermal growth factor receptor #Epithelial–mesenchymal transition #Gefitinib #Gene #Genetics #Internal medicine #Lung Cancer Treatments and Mutations #Lung cancer #Medicine #Mesenchymal stem cell #Metastasis #Oncology #Pathology #RNA modifications and cancer #Transition (genetics)
paper · pdf · doi:10.18632/aging.206086
openalex publication_date 2024/09/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
EGFR-TKIs have been used as frontline treatment in patients with advanced non-small cell lung cancer (NSCLC)suffering from the EGFR mutation.Gefitinib, the first-generation EGFR-TKI, has greatly improved survival rates in lung cancer patients, whereas acquired gefitinib resistance is still a critical issue that needs to be overcome.In our research, high expression levels of CIB2 were found in gefitinib-resistant lung cancer cells.CIB2 knockout rendered gefitinib-resistant cells more sensitive to gefitinib, and overexpression of CIB2 in parental cells was sufficient to induce more resistance to gefitinib.Inhibition of CIB2 in gefitinib-resistant lung cancer cells significantly induced cell apoptosis.To clarify the major molecular mechanism by which CIB2 increases gefitinib resistance, we demonstrated that raised CIB2 in lung cancer cells promoted epithelial-to-mesenchymal transition (EMT) through upregulation of ZEB1.Moreover, FOSL1 transcriptionally regulated CIB2 expression.Finally, CIB2 rendered tumors resistant to gefitinib treatment in vivo.Our results explored a new mechanism: upregulated CIB2 promoted EMT through ZEB1 to regulate gefitinib resistance, which could be a candidate therapeutic target for overcoming acquired resistance to EGFR-TKIs in NSCLC patients.