Blocking ROR1 enhances the roles of erlotinib in lung adenocarcinoma cell lines

doi:10.3892/ol.2019.10643

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	Blocking ROR1 enhances the roles of erlotinib in lung adenocarcinoma cell lines
	Wang, Hui-Li 1; Liu, Yan-Chun2 ; Long, Ming-Peng 1; Zheng, Chuan 1; Yang, Jia-Hui 1
刊名	ONCOLOGY LETTERS
	2019-09-01
卷号	18 期号:3 页码:2977-2984
关键词	receptor tyrosine kinase-like orphan receptor 1 lung adenocarcinoma erlotinib resistance AKT mammalian target of rapamycin small interfering RNA
ISSN号	1792-1074
DOI	10.3892/ol.2019.10643
通讯作者	Zheng, Chuan(alonzc@163.com) ; Yang, Jia-Hui(yangjiahui@cdutcm.edu.cn)
英文摘要	Treatment strategies involving tyrosine kinase inhibitors (TKIs) for patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations have advanced significantly; however, challenges still remain regarding the development of resistance. It has been reported that receptor tyrosine kinase-like orphan receptor 1 (ROR1) acts as a hepatocyte growth factor receptor (MET) and c-Src substrate, and that the extracellular domain of ROR1 is associated with EGFR to sustain EGFR-ERBB3-PI3K signaling. Our previous study reported that blocking ROR1 significantly decreased the activity of key signal molecules in the AKT/mammalian target of rapamycin (mTOR) signaling pathway, which was associated with a significant increase of apoptosis and significant decrease of proliferation of lung adenocarcinoma cells. The present study hypothesized that inhibiting ROR1 could potentially prevent erlotinib resistance in NSCLC cell lines. Investigations were performed with two erlotinib-resistant cell lines XLA-07 and NCI-H1975, and an erlotinib-acquired-resistant cell line PC-9erlo, which was developed from its parental cell line PC-9. It was identified that the inhibition of ROR1 via small interfering RNA treatment significantly improved the anti-proliferation and apoptosis-inducing roles of erlotinib in TKI-resistant tumor cells. This was in accordance with the activity of key molecules of the AKT/mTOR signaling pathway, including glycogen synthase kinase-3 alpha/beta (GSK-3 alpha/beta), phosphatase and tensin homolog (PTEN), AKT, mTOR and ribosomal protein S6 kinase beta-1 (p70S6K). The current data suggest that targeting ROR1 is a potential novel treatment strategy for patients with ROR1-positive NSCLC, particularly those with acquired resistance to EGFR-TKI.
WOS研究方向	Oncology
语种	英语
WOS记录号	WOS:000487675500101
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn/handle/151853/69449]
专题	昆明植物研究所_植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Zheng, Chuan; Yang, Jia-Hui
作者单位	1.Chengdu Univ Tradit Chinese Med, Sch Basic Med, 1166 Liutai Ave, Chengdu 611137, Sichuan, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Wang, Hui-Li,Liu, Yan-Chun,Long, Ming-Peng,et al. Blocking ROR1 enhances the roles of erlotinib in lung adenocarcinoma cell lines[J]. ONCOLOGY LETTERS,2019,18(3):2977-2984.
APA	Wang, Hui-Li,Liu, Yan-Chun,Long, Ming-Peng,Zheng, Chuan,&Yang, Jia-Hui.(2019).Blocking ROR1 enhances the roles of erlotinib in lung adenocarcinoma cell lines.ONCOLOGY LETTERS,18(3),2977-2984.
MLA	Wang, Hui-Li,et al."Blocking ROR1 enhances the roles of erlotinib in lung adenocarcinoma cell lines".ONCOLOGY LETTERS 18.3(2019):2977-2984.