RRC ID 68838
著者 Nanamiya R, Saito-Koyama R, Miki Y, Inoue C, Asavasupreechar T, Abe J, Sato I, Sasano H.
タイトル EphB4 as a Novel Target for the EGFR-Independent Suppressive Effects of Osimertinib on Cell Cycle Progression in Non-Small Cell Lung Cancer.
ジャーナル Int J Mol Sci
Abstract Osimertinib is the latest generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor used for patients with EGFR-mutated non-small cell lung cancer (NSCLC). We aimed to explore the novel mechanisms of osimertinib by particularly focusing on EGFR-independent effects, which have not been well characterized. We explored the EGFR-independent effects of osimertinib on cell proliferation using NSCLC cell lines, an antibody array analysis, and the association between the action of osimertinib and the ephrin receptor B4 (EphB4). We also studied the clinicopathological significance of EphB4 in 84 lung adenocarcinoma patients. Osimertinib exerted significant inhibitory effects on cell growth and cell cycle progression by promoting the phosphorylation of p53 and p21 and decreasing cyclin D1 expression independently of EGFR. EphB4 was significantly suppressed by osimertinib and promoted cell growth and sensitivity to osimertinib. The EphB4 status in carcinoma cells was positively correlated with tumor size, T factor, and Ki-67 labeling index in all patients and was associated with poor relapse-free survival in EGFR mutation-positive patients. EphB4 is associated with the EGFR-independent suppressive effects of osimertinib on cell cycle and with a poor clinical outcome. Osimertinib can exert significant growth inhibitory effects in EGFR-mutated NSCLC patients with a high EphB4 status.
巻・号 22(16)
公開日 2021-8-7
DOI 10.3390/ijms22168522
PII ijms22168522
PMID 34445227
PMC PMC8395224
MeSH A549 Cells Acrylamides / pharmacology* Adenocarcinoma of Lung* / drug therapy Adenocarcinoma of Lung* / genetics Adenocarcinoma of Lung* / metabolism Adenocarcinoma of Lung* / mortality Aniline Compounds / pharmacology* Carcinoma, Non-Small-Cell Lung* / drug therapy Carcinoma, Non-Small-Cell Lung* / genetics Carcinoma, Non-Small-Cell Lung* / metabolism Carcinoma, Non-Small-Cell Lung* / mortality Cell Cycle / drug effects* Cell Cycle / genetics ErbB Receptors / genetics ErbB Receptors / metabolism Humans Lung Neoplasms* / drug therapy Lung Neoplasms* / genetics Lung Neoplasms* / metabolism Lung Neoplasms* / mortality Mutation Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Receptor, EphB4 / genetics Receptor, EphB4 / metabolism*
IF 4.556
リソース情報
ヒト・動物細胞 PC-9(RCB4455)