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Targeting the c-Met/FZD8 Signaling Axis Eliminates Patient-Derived Cancer Stem-like Cells in Head and Neck Squamous Carcinomas
文献类型：期刊论文
| 作者 | Sun, Shuyang; Liu, Suling; Duan, ShengZhong（段胜仲） ; Zhang, Lei; Zhou, Henghua; Hu, Yongjie; Zhou, Xianghui; Shi, Chaoji; Zhou, Rong; Zhang, Zhiyuan
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| 刊名 | CANCER RESEARCH
 |
| 出版日期 | 2014 |
| 卷号 | 74期号:24页码:7546-7559 |
| 英文摘要 | Cancer stem-like cells (CSC) thought to contribute to head and neck squamous carcinomas (HNSCC) may offer attractive therapeutic targets if a tractable approach can be developed. In this study, we report that silencing c-Met is sufficient to suppress sphere formation, tumor initiation, and metastatic properties of HN-CSC. Pharmacologic inhibition of c-Met with the selective inhibitor PF-2341066 preferentially targeted CSC and synergized with conventional chemotherapy to improve efficacy in a mouse xenograft model of HNSCC, impeding tumor growth and reducing metastasis. Mechanistic investigations showed that CSC elimination was due to downregulation of Wnt/beta-catenin signaling in HN-CSC and that the Wnt pathway receptor FZD8 was essential for interactions of c-Met and Wnt/beta-catenin signaling in HN-CSC. Notably, ectopic expression of FZD8 rescued the impaired phenotype of HN-CSC where c-Met was inhibited. Furthermore, c-Met upregulated FZD8 through the ERK/c-Fos cascade in HN-CSC. Taken together, our results offer a preclinical proof-of-concept for targeting the c-Met/FZD8 signaling axis as a CSC-directed therapy to improve HNSCC treatment. (C)2014 AACR. |
| 类目[WOS] | Oncology |
| 研究领域[WOS] | Oncology |
| 关键词[WOS] | BREAST-CANCER ; COLORECTAL-CANCER ; THERAPEUTIC TARGET ; NEGATIVE REGULATOR ; SELF-RENEWAL ; C-MET ; IDENTIFICATION ; RECEPTOR ; PROMOTES ; MARKER |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000346363900037 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/174]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_核受体与代谢和疾病研究组 |
| 推荐引用方式 GB/T 7714 | Sun, Shuyang,Liu, Suling,Duan, ShengZhong,et al. Targeting the c-Met/FZD8 Signaling Axis Eliminates Patient-Derived Cancer Stem-like Cells in Head and Neck Squamous Carcinomas[J]. CANCER RESEARCH,2014,74(24):7546-7559. |
| APA | Sun, Shuyang.,Liu, Suling.,Duan, ShengZhong.,Zhang, Lei.,Zhou, Henghua.,...&Zhang, Zhiyuan.(2014).Targeting the c-Met/FZD8 Signaling Axis Eliminates Patient-Derived Cancer Stem-like Cells in Head and Neck Squamous Carcinomas.CANCER RESEARCH,74(24),7546-7559. |
| MLA | Sun, Shuyang,et al."Targeting the c-Met/FZD8 Signaling Axis Eliminates Patient-Derived Cancer Stem-like Cells in Head and Neck Squamous Carcinomas".CANCER RESEARCH 74.24(2014):7546-7559. |
入库方式： OAI收割
来源：上海营养与健康研究所
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