Alanine catabolism as a targetable vulnerability for MYC-driven liver cancer.

ABSTRACT: Liver cancer is a leading cause of cancer-related death world-wide in part due to the shortage of effective therapies, and MYC overexpression defines an aggressive and especially difficult to treat subset of patients. Given MYC's ability to reprogram cancer cell metabolism, and the liver's role as a coordinator of systemic metabolism, we hypothesized that MYC induces metabolic dependencies that could be targeted to attenuate liver tumor growth. We discovered that MYC-driven liver cancers catabolize alanine in a GPT2-dependent manner to sustain their growth. GPT2 is the predominant alanine-catabolizing enzyme expressed in MYC-driven liver tumors and genetic ablation of GPT2 limited MYC-driven liver tumorigenesis. In vivo isotope tracing studies uncovered a role for alanine as a subst

SUBMITTER: Montoya T 

PROVIDER: S-EPMC12324391 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature