Isotope tracing in adult zebrafish reveals alanine cycling between melanoma and liver.

ABSTRACT: The cell-intrinsic nature of tumor metabolism has become increasingly well characterized. The impact that tumors have on systemic metabolism, however, has received less attention. Here, we used adult zebrafish harboring BRAF^V600E-driven melanoma to study the effect of cancer on distant tissues. By applying metabolomics and isotope tracing, we found that melanoma consume ~15 times more glucose than other tissues measured. Despite this burden, circulating glucose levels were maintained in disease animals by a tumor-liver alanine cycle. Excretion of glucose-derived alanine from tumors provided a source of carbon for hepatic gluconeogenesis and allowed tumors to remove excess nitrogen from branched-chain amino acid catabolism, which we found to be activated in zebrafish and human me

SUBMITTER: Naser FJ 

PROVIDER: S-EPMC9275394 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature