The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss

	The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss
	Feng, Y; Wang, Y; Wang, ZY; Fang, ZY; Li, F; Gao, YJ; Liu, HY; Xiao, T; Li, FM; Zhou, Y
刊名	CANCER RESEARCH
	2012
卷号	72 期号:24 页码:6502-6511
通讯作者	Ji, HB (reprint author), Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,hbji@sibs.ac.cn
英文摘要	Somatic mutation of the tumor suppressor gene LKB1 occurs frequently in lung cancer where it causes tumor progression and metastasis, but the underlying mechanisms remain mainly unknown. Here, we show that the oncogene NEDD9 is an important downstream mediator of lung cancer progression evoked by LKB1 loss. In de novo mouse models, RNAi-mediated silencing of Nedd9 inhibited lung tumor progression, whereas ectopic NEDD9 expression accelerated this process. Mechanistically, LKB1 negatively regulated NEDD9 transcription by promoting cytosolic translocation of CRTC1 from the nucleus. Notably, ectopic expression of either NEDD9 or CRTC1 partially reversed the inhibitory function of LKB1 on metastasis of lung cancer cells. In clinical specimens, elevated expression of NEDD9 was associated with malignant progression and metastasis. Collectively, our results decipher the mechanism through which LKB1 deficiency promotes lung cancer progression and metastasis, and provide a mechanistic rationale for therapeutic attack of these processes. Cancer Res; 72(24); 6502-11. (c) 2012 AACR.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	CREB COACTIVATOR TORC2 ; CARCINOMA-CELLS ; FILAMENTATION 1 ; HUMAN ENHANCER ; PROTEIN ; KINASE ; METASTASIS ; EXPRESSION ; MUTATIONS ; GENE
收录类别	SCI
语种	英语
WOS记录号	WOS:000312591900020
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/688]
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	Feng, Y,Wang, Y,Wang, ZY,et al. The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss[J]. CANCER RESEARCH,2012,72(24):6502-6511.
APA	Feng, Y.,Wang, Y.,Wang, ZY.,Fang, ZY.,Li, F.,...&Ji, HB.(2012).The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss.CANCER RESEARCH,72(24),6502-6511.
MLA	Feng, Y,et al."The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss".CANCER RESEARCH 72.24(2012):6502-6511.