Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

Choong-Kun Lee; Seung-Hwan Jeong; Cholsoon Jang; Hosung Bae; Yoo Hyung Kim; Intae Park; Sang Kyum Kim; Gou Young Koh

doi:10.1126/science.aav0173

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Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

Journal article

Peer reviewed

Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation

Choong-Kun Lee, Seung-Hwan Jeong, Cholsoon Jang, Hosung Bae, Yoo Hyung Kim, Intae Park, Sang Kyum Kim and Gou Young Koh

Science (American Association for the Advancement of Science), Vol.363(6427), pp.644-649

02/08/2019

DOI: 10.1126/science.aav0173

PMID: 30733421

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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.

Adaptor Proteins, Signal Transducing - metabolism

Animals

Bile Acids and Salts - metabolism

Cell Cycle Proteins

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

Phosphoproteins - metabolism

PPAR alpha - metabolism

Signal Transduction

Details

Title: Subtitle: Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation
Creators: Choong-Kun Lee - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
Seung-Hwan Jeong - Institute for Basic Science
Cholsoon Jang - Princeton University
Hosung Bae - Korea Advanced Institute of Science and Technology
Yoo Hyung Kim - Korea Advanced Institute of Science and Technology
Intae Park - Korea Advanced Institute of Science and Technology
Sang Kyum Kim - Yonsei University
Gou Young Koh - Korea Advanced Institute of Science and Technology
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.363(6427), pp.644-649
DOI: 10.1126/science.aav0173
PMID: 30733421
NLM abbreviation: Science
ISSN: 0036-8075
eISSN: 1095-9203
Language: English
Date published: 02/08/2019
Academic Unit: Internal Medicine
Record Identifier: 9985217136802771

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