Cigarette smoke-induced LKB1/AMPK pathway deficiency reduces EGFR TKI sensitivity in NSCLC

doi:10.1038/s41388-020-01597-1

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 310902500/24902

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24902

Title:	Cigarette smoke-induced LKB1/AMPK pathway deficiency reduces EGFR TKI sensitivity in NSCLC
Authors:	Cheng, FJ;Chen, CH;Tsai, WC;Wang, BW;Yu, MC;Hsia, TC;Wei, YL;Hsiao, YC;Hu, DW;Ho, CY;Li, TS;Wu, CY;Chou, WY;Yu, YL;Tang, CH;Chen, CY;Chen, CM;Hsu, JL;Chen, HF;Chen, Y;Tu, CY;Hung, MC;Huang, WC
Date:	2021
Issue Date:	2022-08-09T08:09:51Z (UTC)
Publisher:	SPRINGERNATURE
ISSN:	0950-9232
Abstract:	Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFR(WT)) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFR(WT) and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFR(WT).
URI:	http://dx.doi.org/10.1038/s41388-020-01597-1 https://www.webofscience.com/wos/woscc/full-record/WOS:000599788200001 https://ir.csmu.edu.tw:8080/handle/310902500/24902
Relation:	ONCOGENE ,2021 ,v40 ,issue 6 ,p1162-1175
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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