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

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	The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss
	Wang, Y
刊名	CANCER RESEARCH
	2012
卷号	72 期号:24 页码:6502-6511
关键词	CREB COACTIVATOR TORC2 CARCINOMA-CELLS FILAMENTATION 1 HUMAN ENHANCER PROTEIN KINASE METASTASIS EXPRESSION MUTATIONS GENE
ISSN号	0008-5472
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
收录类别	SCI
资助信息	AstraZenca; Millenium; National Basic Research Program of China [2010CB912102, 2012CB910800]; National Natural Science Foundation of China [81101583, 30971461]; postdoctoral foundation [2010KIP504, 2011KIP505]; Shanghai postdoctoral foundation [Y15CS11371, Y149S11371]
语种	英语
公开日期	2013-06-04
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/2502]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Wang, Y. The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss[J]. CANCER RESEARCH,2012,72(24):6502-6511.
APA	Wang, Y.(2012).The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss.CANCER RESEARCH,72(24),6502-6511.
MLA	Wang, Y."The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss".CANCER RESEARCH 72.24(2012):6502-6511.