Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma
文献类型：期刊论文
| 作者 | Han, XK; Li, FM; Fang, ZY; Gao, YJ; Li, F; Fang, R; Yao, S; Sun, YH; Li, L; Zhang, WJ |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2014 |
| 卷号 | 5期号:1页码:3261-3261 |
| 通讯作者 | Ji, HB (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,hbji@sibcb.ac.cn |
| 英文摘要 | Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 关键词[WOS] | PEUTZ-JEGHERS-SYNDROME ; HEMATOPOIETIC STEM-CELLS ; GROWTH-FACTOR RECEPTOR ; LYSYL OXIDASE ; TRANSGENIC MICE ; IN-VIVO ; K-RAS ; BETA-AMINOPROPIONITRILE ; ADENOSQUAMOUS CARCINOMA ; SOMATIC MUTATIONS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000332667600008 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/283]  |
| 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 | Han, XK,Li, FM,Fang, ZY,et al. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma[J]. NATURE COMMUNICATIONS,2014,5(1):3261-3261. |
| APA | Han, XK.,Li, FM.,Fang, ZY.,Gao, YJ.,Li, F.,...&Ji, HB.(2014).Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma.NATURE COMMUNICATIONS,5(1),3261-3261. |
| MLA | Han, XK,et al."Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma".NATURE COMMUNICATIONS 5.1(2014):3261-3261. |
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