E-MTAB-7621 - Tumor metastasis to lymph node requires YAP-dependent metabolic adaptation
Submitted on 31 July 2017, last updated on 8 February 2019, released on 9 February 2019
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.
RNA-seq of coding RNA, disease state design
Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Lee CK, Jeong SH, Jang C, Bae H, Kim YH, Park I, Kim SK, Koh GY. Science 363(6427):644-649 (2019), PMID:30733421