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Science. 2019 Feb 8;363(6427):644-649. doi: 10.1126/science.aav0173. Epub 2019 Feb 7.

Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation.

Lee CK1, Jeong SH1,2, Jang C3, Bae H1,2, Kim YH1,2, Park I1,2, Kim SK4, Koh GY5,2.

Author information

1
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
2
Center for Vascular Research, Institute for Basic Science (IBS), Daejeon 34141, Republic of Korea.
3
Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA.
4
Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
5
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. gykoh@kaist.ac.kr.

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.

PMID:
30733421
DOI:
10.1126/science.aav0173
[Indexed for MEDLINE]

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