Circulating Proteoglycan Endocan Mediates EGFR-Driven Progression of Non-Small Cell Lung Cancer

doi:10.1158/0008-5472.CAN-20-0005

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24808

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24808

Title:	Circulating Proteoglycan Endocan Mediates EGFR-Driven Progression of Non-Small Cell Lung Cancer
Authors:	Yang, YC;Pan, KF;Lee, WJ;Chang, JH;Tan, P;Gu, CC;Chang, WM;Yang, SF;Hsiao, M;Hua, KT;Chien, MH
Date:	2020
Issue Date:	2022-08-09T08:08:19Z (UTC)
Publisher:	AMER ASSOC CANCER RESEARCH
ISSN:	0008-5472
Abstract:	Although new generations of EGFR-tyrosine kinase inhibitors (EGFR-TKI) have been developed for the treatment of patients with non-small cell lung cancer (NSCLC) with EGFR-mutant tumors, TKI resistance often returns as a result of additional EGFR mutations. In addition to seeking for next-generation EGFR-TKI, developing novel EGFR-targeting strategies may hold the key to overcome the vicious cycle of TKI resistance. Endocan is known as a receptor tyrosine kinase ligand enhancer in tumorigenesis, but the impact of endocan on EGFR-driven NSCLC progression remains unknown. In this study, higher endocan levels were found in lung tumors compared with cancer-free tissues and correlated with poor prognosis in patients with NSCLC harboring mutant EGFR; circulating endocan levels were also significantly higher in patients with mutant EGFR. Endocan facilitated EGFR signaling via direct binding and enhancing of the EGF-EGFR interaction and supported the growth of tumors driven by mutated EGFR. Activated EGFR in turn upregulated expression of endocan via JAK/STAT3 and ERK/ELK cascades, thus forming a positive regulatory loop of endocan-EGFR signaling. On the basis of the binding region between endocan and EGFR, we designed therapeutic peptides and demonstrated promising therapeutic effects in xenografts harboring EGFR mutations including TKI-resistant T790M. Together, our findings highlight the novel interaction between endocan and EGFR and new opportunities to effectively target endocan-EGFR regulatory axis in patients with TKI-resistant NSCLC. Significance: Endocan is a novel and critical regulator of EGF/EGFR signaling and serves as an alternative target of EGFR-TKI resistance in NSCLC.
URI:	http://dx.doi.org/10.1158/0008-5472.CAN-20-0005 https://www.webofscience.com/wos/woscc/full-record/WOS:000562958600013 https://ir.csmu.edu.tw:8080/handle/310902500/24808
Relation:	CANCER RESEARCH ,2020 ,v80 ,issue 16 ,p3292-3304
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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