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Functional Cooperation of RKTG with p53 in Tumorigenesis and Epithelial-Mesenchymal Transition
文献类型：期刊论文
| 作者 | Jiang, Yuhui; Xie, Xiaoduo; Li, Zhigang; Wang, Zheng; Zhang, Yixuan; Ling, Zhiqiang; Pan, Yi（潘怡）; Wang, ZhenZhen（王甄真）; Chen, Yan（陈雁）
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| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2011 |
| 卷号 | 71期号:8页码:2959-2968 |
| 英文摘要 | Raf kinase trapping to Golgi (RKTG) is a potential tumor suppressor gene due to its negative roles in regulating Ras/Raf/MEK/ERK (extracellular signal-regulated kinase) pathway and GPCR (G protein-coupled receptor) G beta gamma subunit signaling. Interestingly, RKTG-deficient mice are free of tumors, although they are prone to form skin cancer on carcinogen administration. On the other hand, p53 is a well-characterized tumor suppressor gene and p53 heterozygous mice develop sarcoma and other tumors starting from 12 months of age. In RKTG-null mouse embryonic fibroblasts, lypophosphatidic acid (LPA), but not EGF (epidermal growth factor), could stimulate hyperphosphorylation of AKT and GSK3 beta, accompanied by increases in phosphorylation of p53 at Ser15 and accumulation of p53, as well as its target genes p21 and p16. Spontaneous skin cancer-like tumors were detected in about 25% of RKTG nullizygous and p53 heterozygous mice within 7 months of age. Hyperplasia and epithelial-mesenchymal transition (EMT) were observed in the tumor-overlying epidermis, in which LOH of p53 occurred and EMT features emerged. In p53-mutated A431 epithelial carcinoma cells, knockdown of RKTG led to enhancement of LPA-stimulated AKT and GSK3 beta phosphorylation, together with increased accumulation of beta-catenin and appearance of EMT features that were antagonized by p53 overexpression. In HepG2 epithelial cells, LPA-stimulated AKT phosphorylation and EMT features reached maximum when both RKTG and p53 were simultaneously silenced. In summary, these results not only indicate that RKTG has an in vivo tumor suppressor function to cooperate with p53 in tumorigenesis but also suggest that p53 has an EMT checkpoint function and the loss of this function can combine with loss of RKTG to drive EMT and tumor progression. Cancer Res; 71(8); 2959-68. (C)2011 AACR. |
| 类目[WOS] | Oncology |
| 关键词[WOS] | BETA-CATENIN ; CELL CARCINOMA ; CANCER-CELLS ; E-CADHERIN ; DOWN-REGULATION ; AKT ; ACTIVATION ; PHOSPHORYLATION ; MICE ; INACTIVATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000289507800016 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/77]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_信号转导与营养相关疾病研究组 |
| 推荐引用方式 GB/T 7714 | Jiang, Yuhui,Xie, Xiaoduo,Li, Zhigang,et al. Functional Cooperation of RKTG with p53 in Tumorigenesis and Epithelial-Mesenchymal Transition[J]. CANCER RESEARCH,2011,71(8):2959-2968. |
| APA | Jiang, Yuhui.,Xie, Xiaoduo.,Li, Zhigang.,Wang, Zheng.,Zhang, Yixuan.,...&Chen, Yan.(2011).Functional Cooperation of RKTG with p53 in Tumorigenesis and Epithelial-Mesenchymal Transition.CANCER RESEARCH,71(8),2959-2968. |
| MLA | Jiang, Yuhui,et al."Functional Cooperation of RKTG with p53 in Tumorigenesis and Epithelial-Mesenchymal Transition".CANCER RESEARCH 71.8(2011):2959-2968. |
入库方式： OAI收割
来源：上海营养与健康研究所
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