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DOI | 10.1126/science.aav0173 |
Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation | |
Lee, Choong-kun1; Jeong, Seung-hwan1,2; Jang, Cholsoon3,4; Bae, Hosung1,2; Kim, Yoo Hyung1,2; Park, Intae1,2; Kim, Sang Kyum5; Koh, Gou Young1,2 | |
2019-02-08 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 363期号:6427页码:644-+ |
文章类型 | Article |
语种 | 英语 |
国家 | South Korea; USA |
英文摘要 | In cancer patients, metastasis of tumors to sentinel lymph nodes (LNs) predicts disease progression and often guides treatment decisions. The mechanisms underlying tumor LN metastasis are poorly understood. By using comparative transcriptomics and metabolomics analyses of primary and LN-metastatic tumors in mice, we found that LN metastasis requires that tumor cells undergo a metabolic shift toward fatty acid oxidation (FAO). Transcriptional coactivator yes-associated protein (YAP) is selectively activated in LN-metastatic tumors, leading to the up-regulation of genes in the FAO signaling pathway. Pharmacological inhibition of FAO or genetic ablation of YAP suppressed LN metastasis in mice. Several bioactive bile acids accumulated to high levels in the metastatic LNs, and these bile acids activated YAP in tumor cells, likely through the nuclear vitamin D receptor. Inhibition of FAO or YAP may merit exploration as a potential therapeutic strategy for mitigating tumor metastasis to LNs. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000458114200052 |
WOS关键词 | BLOOD-VESSELS ; BILE-ACIDS ; DISSEMINATION ; MAMMARY ; EXIT |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200714 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon 34141, South Korea; 2.Inst for Basic Sci Korea, Ctr Vasc Res, Daejeon 34141, South Korea; 3.Princeton Univ, Lewis Sigler Inst Integrat Genom, Washington Rd, Princeton, NJ 08544 USA; 4.Princeton Univ, Dept Chem, Washington Rd, Princeton, NJ 08544 USA; 5.Yonsei Univ, Dept Pathol, Coll Med, Seoul 03722, South Korea |
推荐引用方式 GB/T 7714 | Lee, Choong-kun,Jeong, Seung-hwan,Jang, Cholsoon,et al. Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation[J]. SCIENCE,2019,363(6427):644-+. |
APA | Lee, Choong-kun.,Jeong, Seung-hwan.,Jang, Cholsoon.,Bae, Hosung.,Kim, Yoo Hyung.,...&Koh, Gou Young.(2019).Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation.SCIENCE,363(6427),644-+. |
MLA | Lee, Choong-kun,et al."Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation".SCIENCE 363.6427(2019):644-+. |
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