PKC delta-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs

doi:doi.org/10.1038/s41388-021-01889-0

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學研究所 > 期刊論文 > Item 310902500/21597

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題名:	PKC delta-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs
作者:	Chen, Chia-Hung Wang, Bo-Wei Hsiao, Yu-Chun Wu, Chun-Yi Cheng, Fang-Ju Hsia, Te-Chun Chen, Chih-Yi Wang, Yihua Weihua, Zhang Chou, Ruey-Hwang Tang, Chih-Hsin Chen, Yun-Ju Wei, Ya-Ling Hsu, Jennifer L. Tu, Chih-Yen Hung, Mien-Chie Huang, Wei-Chien
貢獻者:	中山醫學大學;醫研所
關鍵詞:	GROWTH-FACTOR RECEPTOR;TYROSINE KINASE INHIBITOR;BREAST-CANCER CELLS;LUNG-CANCER;GLUCOSE-TRANSPORTER;EARLY;PREDICTION;EXPRESSION;PROTEIN;PHOSPHORYLATION;OVEREXPRESSION
日期:	2021-07-22
上傳時間:	2021-08-11T05:58:17Z (UTC)
出版者:	ONCOGENE
ISSN:	0950-9232
摘要:	The tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have been widely used for non-small cell lung cancer (NSCLC) patients, but the development of acquired resistance remains a therapeutic hurdle. The reduction of glucose uptake has been implicated in the anti-tumor activity of EGFR TKIs. In this study, the upregulation of the active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with the poorer clinical outcome of the NSCLC patients who received EGFR TKI treatment. Blockade of SGLT1 overcame this resistance in vitro and in vivo by reducing glucose uptake in NSCLC cells. Mechanistically, SGLT1 protein was stabilized through the interaction with PKC delta-phosphorylated (Thr678) EGFR in the TKI-resistant cells. Our findings revealed that PKC delta/EGFR axis-dependent SGLT1 upregulation was a critical mechanism underlying the acquired resistance to EGFR TKIs. We suggest co-targeting PKC delta/SGLT1 as a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/21597
關聯:	Oncogene,volume 40
顯示於類別:	[醫學研究所] 期刊論文

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