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Title: The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss
Author: Feng, Y ; null(熊志奇) ; Wang, ZY ; Fang, ZY ; Li, F ; Gao, YJ ; Liu, HY ; Xiao, T ; Li, FM ; Zhou, Y ; Zhai, QW ; Liu, XL ; Sun, YH ; Bardeesy, N ; Wong, KK ; Chen, HQ ; Xiong, ZQ ; Ji, HB
Source: CANCER RESEARCH
Issued Date: 2012
Volume: 72, Issue:24, Pages:6502-6511
Keyword: CREB COACTIVATOR TORC2 ; CARCINOMA-CELLS ; FILAMENTATION 1 ; HUMAN ENHANCER ; PROTEIN ; KINASE ; METASTASIS ; EXPRESSION ; MUTATIONS ; GENE
Subject: Oncology
Corresponding Author: 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
English Abstract: 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.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/2502
Appears in Collections:神经所(总)_期刊论文

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Recommended Citation:
Feng, Y; Wang, Y; Wang, ZY; Fang, ZY; Li, F; Gao, YJ; Liu, HY; Xiao, T; Li, FM; Zhou, Y; Zhai, QW; Liu, XL; Sun, YH; Bardeesy, N; Wong, KK; Chen, HQ; Xiong, ZQ; Ji, HB.The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss,CANCER RESEARCH,2012,72(24):6502-6511
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