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Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

Authors
 Choong-kun Lee  ;  Seung-hwan Jeong  ;  Cholsoon Jang  ;  Hosung Bae  ;  Yoo Hyung Kim  ;  Intae Park  ;  Sang Kyum Kim  ;  Gou Young Koh 
Citation
 Science, Vol.363(6427) : 644-649, 2019 
Journal Title
 Science 
ISSN
 0036-8075 
Issue Date
2019
MeSH
Adaptor Proteins, Signal Transducing/metabolism* ; Animals ; Bile Acids and Salts/metabolism ; Cell Line, Tumor ; Fatty Acids/metabolism* ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Lipid Metabolism ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology* ; Male ; Melanoma, Experimental/metabolism* ; Melanoma, Experimental/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Oxidation-Reduction ; PPAR alpha/metabolism ; Phosphoproteins/metabolism* ; Signal Transduction*
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.
Full Text
https://science.sciencemag.org/content/363/6427/644.long
DOI
10.1126/science.aav0173
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sang Kyum(김상겸) ORCID logo https://orcid.org/0000-0003-0768-9923
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171141
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