Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

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Title
Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation
Author(s)
Lee C.-K.; Seung-hwan Jeong; Jang C.; Hosung Bae; Yoo Hyung Kim; Intae Park; Kim S.K.; Gou Young Koh
Publication Date
2019
Journal
SCIENCE, v.363, no.6427, pp.644 - 649
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
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. 2017 © The Authors
URI
https://pr.ibs.re.kr/handle/8788114/5768
ISSN
0036-8075
Appears in Collections:
Center for Cardiovascular Research(혈관 연구단) > Journal Papers (저널논문)
Files in This Item:
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