TROY Modulates Cancer Stem-Like Cell Properties and Gefitinib Resistance Through EMT Signaling in Non–Small Cell Lung Cancer

Frontiers in Genetics

Yuman Yu¹  Xiaoling Wang²  Liming Xu²  Yuehong Wang³  Jianying Zhou³  Linying Wu³ 

[1] Department of Geriatrics, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China;Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China;Department of Respiratory Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China;

关键词: non–small cell lung cancer;    drug resistance;    TROY;    epithelial–mesenchymal transition;    RNA sequencing;    cancer stem-like cells;   

DOI  :  10.3389/fgene.2022.881875

来源: DOAJ

【 摘 要 】

Targeted therapy has made breakthrough progress in the treatment of advanced non–small cell lung cancer (NSCLC) in the last 20 years. Despite that, acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is an urgent clinical problem. Our study established an acquired gefitinib-resistant cell line, which exhibited epithelial–mesenchymal transition (EMT) and stem cell–like properties. Transcriptional sequencing and bioinformatics analysis revealed that TROY was significantly increased in gefitinib-resistant cells. Gene set enrichment analysis (GSEA) showed EMT was the core enriched hallmark in the resistant cells. TROY siRNA interference could overcome the gefitinib resistance with the downregulated expression of EMT and CSC markers. In addition, immunohistochemistry indicated that TROY was overexpressed in tumor samples from patients who acquired resistance to first-generation EGFR-TKI without T790M mutation and the expression of TROY was associated with poor prognosis in LUAD. Here, we provided the potential role of TROY in the resistance of targeted therapy and a new strategy to overcome the acquired resistance to EGFR-TKI in NSCLC.

【 授权许可】

Unknown