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RACK1 Suppresses Gastric Tumorigenesis by Stabilizing the beta-Catenin Destruction Complex
文献类型：期刊论文
| 作者 | Deng, Yue-Zhen; Yao, Fan; Li, Jing-Jing; Mao, Zheng-Fa; Hu, Ping-Ting; Long, Ling-Yun; Li, Guo; Ji, Xiao-Dan; Shi, Shuo; Guan, Dong-Xian |
| 刊名 | GASTROENTEROLOGY
 |
| 出版日期 | 2012 |
| 卷号 | 142期号:4页码:812-U246 |
| 关键词 | Dvl2 Tumor Suppressor GNB2L1 Stomach Cancer |
| 通讯作者 | Xie, D (reprint author), Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab, 294 Tai Yun Rd, Shanghai 20031, Peoples R China. |
| 英文摘要 | BACKGROUND & AIMS: Dysregulation of Wnt signaling has been involved in gastric tumorigenesis by mechanisms that are not fully understood. The receptor for activated protein kinase C (RACK1, GNB2L1) is involved in development of different tumor types, but its expression and function have not been investigated in gastric tumors. METHODS: We analyzed expression of RACK1 in gastric tumor samples and their matched normal tissues from 116 patients using immunohistochemistry. Effects of knockdown with small interfering RNAs or overexpression of RACK1 in gastric cancer cell lines were evaluated in cell growth and tumor xenograft. RACK1 signaling pathways were investigated in cells and zebrafish embryos using immunoblot, immunoprecipitation, microinjection, and in situ hybridization assays. RESULTS: Expression of RACK1 was reduced in gastric tumor samples and correlated with depth of tumor infiltration and poor differentiation. Knockdown of RACK1 in gastric cancer cells accelerated their anchorage-independent proliferation in soft agar, whereas overexpression of RACK1 reduced their tumorigenicity in nude mice. RACK1 formed a complex with glycogen synthase kinase Gsk3 beta and Axin to promote the interaction between Gsk3 beta and beta-catenin and thereby stabilized the beta-catenin destruction complex. On stimulation of Wnt3a, RACK1 repressed Wnt signaling by inhibiting recruitment of Axin by Dishevelled 2 (Dvl2). Moreover, there was an inverse correlation between expression of RACK1 and localization of beta-catenin to the cytoplasm/nucleus in human gastric tumor samples. CONCLUSIONS: RACK1 negatively regulates Wnt signaling pathway by stabilizing the beta-catenin destruction complex and act as a tumor suppressor in gastric cancer cells. |
| 类目[WOS] | Gastroenterology & Hepatology |
| 研究领域[WOS] | Gastroenterology & Hepatology |
| 关键词[WOS] | HELICOBACTER-PYLORI ; SCAFFOLD PROTEIN ; EPITHELIAL-CELLS ; TUMOR-SUPPRESSOR ; GROWTH-FACTOR ; SRC ACTIVITY ; WNT ; EXPRESSION ; GENE ; ACTIVATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000302296400031 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/285]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 推荐引用方式 GB/T 7714 | Deng, Yue-Zhen,Yao, Fan,Li, Jing-Jing,et al. RACK1 Suppresses Gastric Tumorigenesis by Stabilizing the beta-Catenin Destruction Complex[J]. GASTROENTEROLOGY,2012,142(4):812-U246. |
| APA | Deng, Yue-Zhen.,Yao, Fan.,Li, Jing-Jing.,Mao, Zheng-Fa.,Hu, Ping-Ting.,...&Xie, Dong.(2012).RACK1 Suppresses Gastric Tumorigenesis by Stabilizing the beta-Catenin Destruction Complex.GASTROENTEROLOGY,142(4),812-U246. |
| MLA | Deng, Yue-Zhen,et al."RACK1 Suppresses Gastric Tumorigenesis by Stabilizing the beta-Catenin Destruction Complex".GASTROENTEROLOGY 142.4(2012):812-U246. |
入库方式： OAI收割
来源：上海营养与健康研究所
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