Science 363, 644–649 (2019)

The metastatic potential of primary tumor cells greatly increases after they migrate to draining lymph nodes (LNs). In Science, Lee et al. report that tumor cells adapt to this fatty-acid-rich environment by altering their cellular metabolism to fatty-acid oxidation. The transcription factor YAP is activated and translocates to the nucleus in LN-resident tumor cells but not primary tumors or distal sites of metastasis. Bile acids produced as cholesterol metabolites within the LN environment promote this response. Inhibition of fatty-acid oxidation or small interfering RNA–mediated knockdown of YAP or the bile-converting enzyme CYP7A1 in tumor cells diminishes their metastatic potential in LNs. Notably, in a small cohort of patients with tumors, the nuclear localization of YAP in tumors that have metastasized to the LNs also correlates with reduced survival. These findings show that tumor cells can adapt their metabolism to their local environment.