Epithelial-mesenchymal transition is associated with osteopontin- induced EGFR-TKI resistance in EGFR mutant non-small cell lung cancer

doi:10.21037/jtd-23-818

科研成果详情

题名	Epithelial-mesenchymal transition is associated with osteopontin- induced EGFR-TKI resistance in EGFR mutant non-small cell lung cancer
作者	Chen, Junjie 1; Shi, Lin 2; Qian, Yao1; Jin, Yi3; Dong, Nian 1; Chen, Chengshui 1; Wang, Beibei 1
发表日期	2023-06-26
发表期刊	JOURNAL OF THORACIC DISEASE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Osteopontin (OPN) epithelial-mesenchymal transition (EMT) epidermal growth factor receptor-tyrosine kinase inhibitor resistance (EGFR-TKI resistance) phosphatidylinositol-3 kinase protein kinase B (PI3K AKT) non-small cell lung cancer (NSCLC)
其他关键词	PHASE-III ; 1ST-LINE TREATMENT ; OPEN-LABEL ; CHEMOTHERAPY ; MUTATION ; ERLOTINIB ; AFATINIB ; ADENOCARCINOMA ; OSIMERTINIB ; MULTICENTER
摘要	Background: Resistance restricts the long-term therapeutic efficacy of epidermal growth factor receptortyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer (NSCLC) with positive EGFR mutations. The present study sought to identify the potential protein osteopontin (OPN) involved in EGFR-TKI resistance and examine its therapeutic mechanism in NSCLC.Methods: The expression of OPN in NSCLC tissues was evaluated by immunohistochemistry (IHC). Western blot (WB), quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence staining were used to analyze OPN and epithelial-mesenchymal transition (EMT)-related protein expression in the PC9 and PC9 gefitinib resistance (PC9GR) cells. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the secreted OPN. Cell Counting Kit-8 (CCK-8) assays and flow cytometry were used to examine the effect of OPN on the gefitinib-induced growth and death of PC9 or PC9GR cells.Results: OPN was upregulated in the human NSCLC tissues and cells resistant to EGFR-TKIs. The overexpression of OPN inhibited EGFR-TKI-induced apoptosis and was associated with the formation of EMT. By activating the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)-EMT pathway, OPN contributed to the development of EGFR-TKI resistance. Reducing OPN expression and inhibiting PI3K/ AKT signaling improved EGFR-TKI sensitivity significantly more than the use of either agent alone.Conclusions: This study showed that OPN increased EGFR-TKI resistance in NSCLC through the OPN-PI3K/AKT-EMT pathway. Our findings may provide a possible therapeutic target for overcoming EGFR-TKI resistance in this pathway.
资助项目	Basic Scientific Research Program of Wenzhou[Y20190207,Y20190522,Y20220341];Key Laboratory of Interventional Pulmonology of Zhejiang Province[2019E10014];Outstanding Youth Foundation of Zhongshan Hospital[2021ZSYQ25];National Nature Science Foundation of China[81800034];Natural Science Foundation of Zhejiang Province[LQ20H010002];Health Science and Technology Project of Zhejiang Province[2022RC047,Y20220038];
出版者	AME PUBLISHING COMPANY
ISSN	2072-1439
EISSN	2077-6624
卷号	15 期号:6 页码:3359-3371
DOI	10.21037/jtd-23-818
页数	14
WOS类目	Respiratory System
WOS研究方向	Respiratory System
WOS记录号	WOS:001019539800001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	37426126
SCOPUSEID	2-s2.0-85166242441
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/181608
专题	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科附属第一医院_病理科
通讯作者	Chen, Chengshui; Wang, Beibei
作者单位	1.Wenzhou Med Univ, Dept Pulm & Crit Care Med, Key Lab Intervent Pulmonol Zhejiang Prov, Affiliated Hosp 1, Wenzhou 325006, Peoples R China; 2.Fudan Univ, Zhongshan Hosp, Dept Pulm & Crit Care Med, Shanghai, Peoples R China; 3.Wenzhou Med Univ, Pathol Dept, Affiliated Hosp 1, Wenzhou, Peoples R China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科
推荐引用方式 GB/T 7714	Chen, Junjie,Shi, Lin,Qian, Yao,et al. Epithelial-mesenchymal transition is associated with osteopontin- induced EGFR-TKI resistance in EGFR mutant non-small cell lung cancer[J]. JOURNAL OF THORACIC DISEASE,2023,15(6):3359-3371.
APA	Chen, Junjie., Shi, Lin., Qian, Yao., Jin, Yi., Dong, Nian., ... & Wang, Beibei. (2023). Epithelial-mesenchymal transition is associated with osteopontin- induced EGFR-TKI resistance in EGFR mutant non-small cell lung cancer. JOURNAL OF THORACIC DISEASE, 15(6), 3359-3371.
MLA	Chen, Junjie,et al."Epithelial-mesenchymal transition is associated with osteopontin- induced EGFR-TKI resistance in EGFR mutant non-small cell lung cancer".JOURNAL OF THORACIC DISEASE 15.6(2023):3359-3371.