LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response

	LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response
	Li, FM; Han, XK; Li, F; Wang, R; Wang, H; Gao, YJ; Wang, XJ; Fang, ZY; Zhang, WJ; Yao, S
刊名	CANCER CELL
	2015
卷号	27 期号:5 页码:698-711
通讯作者	Chen, HQ (reprint author), Fudan Univ, Shanghai Canc Ctr, Dept Thorac Surg, Shanghai 200032, Peoples R China.,hqchen1@yahoo.com
英文摘要	LKB1 regulates both cell growth and energy metabolism. It remains unclear how LKB1 inactivation coordinates tumor progression with metabolic adaptation in non-small cell lung cancer (NSCLC). Here in Kras(G12D); Lkb1(lox/lox) (KL) mouse model, we reveal differential reactive oxygen species (ROS) levels in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). ROS can modulate ADC-to-SCC transdifferentiation (AST). Further, pentose phosphate pathway deregulation and impaired fatty acid oxidation collectively contribute to the redox imbalance and functionally affect AST. Similar tumor and redox heterogeneity also exist in human NSCLC with LKB1 inactivation. In preclinical trials toward metabolic stress, certain KL ADC can develop drug resistance through squamous transdifferentiation. This study uncovers critical redox control of tumor plasticity that may affect therapeutic response in NSCLC.
学科主题	Oncology ; Cell Biology
类目[WOS]	Oncology ; Cell Biology
关键词[WOS]	HEMATOPOIETIC STEM-CELLS ; LKB1-AMPK PATHWAY ; NEVER-SMOKERS ; K-RAS ; ADENOCARCINOMA ; METABOLISM ; MICE ; HOMEOSTASIS ; EXPRESSION ; STRESS
收录类别	SCI
语种	英语
WOS记录号	WOS:000354287300011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/62]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, FM,Han, XK,Li, F,et al. LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response[J]. CANCER CELL,2015,27(5):698-711.
APA	Li, FM.,Han, XK.,Li, F.,Wang, R.,Wang, H.,...&Ji, HB.(2015).LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response.CANCER CELL,27(5),698-711.
MLA	Li, FM,et al."LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response".CANCER CELL 27.5(2015):698-711.