Transcriptomics

Dataset Information

22

Tumor metastasis to lymph node requires YAP-dependent metabolic adaptation


ABSTRACT: In cancer patients, metastasis of tumors to sentinel lymph nodes (LN) predicts disease progression and often guides treatment decisions. The mechanisms underlying tumor LN metastasis are poorly understood. 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 co-activator yes-associated protein (YAP) is selectively activated in LN metastatic tumors, leading to upregulation 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 were highly accumulated in the LN metastatic tumor. Inhibition of FAO or YAP may merit exploration as therapeutic strategies for mitigating tumor LN metastasis.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Mus musculus  

SUBMITTER: Choong-kun Lee  

PROVIDER: E-MTAB-7621 | ArrayExpress | 2019-02-09

SECONDARY ACCESSION(S): ERP113457

REPOSITORIES: ArrayExpress, ENA

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Publications

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

Lee Choong-Kun CK   Jeong Seung-Hwan SH   Jang Cholsoon C   Bae Hosung H   Kim Yoo Hyung YH   Park Intae I   Kim Sang Kyum SK   Koh Gou Young GY  

Science (New York, N.Y.) 20190207 6427


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 selectivel  ...[more]

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