The CRTC1-NEDD9 Signaling Axis Mediates Lung Cancer Progression Caused by LKB1 Loss
文献类型：期刊论文
| 作者 | Wang, Y
|
| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 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 |
| 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. |
入库方式： OAI收割
来源：上海神经科学研究所
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