Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

Research output: Contribution to journalArticle

Authors

  • Choong kun Lee
  • Seung hwan Jeong
  • Cholsoon Jang
  • Hosung Bae
  • Yoo Hyung Kim
  • Intae Park
  • Sang Kyum Kim
  • Gou Young Koh

External Institution(s)

  • Korea Advanced Institute of Science and Technology
  • Institute for Basic Science
  • Yonsei University

Details

Original languageEnglish (US)
Pages (from-to)644-649
Number of pages6
JournalScience
Volume363
Issue number6427
StatusPublished - Feb 8 2019
Peer-reviewedYes

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.

Citation formats

APA

Lee, C. K., Jeong, S. H., Jang, C., Bae, H., Kim, Y. H., Park, I., ... Koh, G. Y. (2019). Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Science, 363(6427), 644-649. https://doi.org/10.1126/science.aav0173

Harvard

Lee, CK, Jeong, SH, Jang, C, Bae, H, Kim, YH, Park, I, Kim, SK & Koh, GY 2019, 'Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation', Science, vol. 363, no. 6427, pp. 644-649. https://doi.org/10.1126/science.aav0173