Hypoxia-mediated repression of pyruvate carboxylase drives immunosuppression.

ABSTRACT:

Background

Metabolic plasticity mediates breast cancer survival, growth, and immune evasion during metastasis. However, how tumor cell metabolism is influenced by and feeds back to regulate breast cancer progression are not fully understood. We identify hypoxia-mediated suppression of pyruvate carboxylase (PC), and subsequent induction of lactate production, as a metabolic regulator of immunosuppression.

Methods

We used qPCR, immunoblot, and reporter assays to characterize repression of PC in hypoxic primary tumors. Steady state metabolomics were used to identify changes in metabolite pools upon PC depletion. In vivo tumor growth and metastasis assays were used to evaluate the impact of PC manipulation and pharmacologic inhibition of lactate transporters. Immunohistochemistr

SUBMITTER: Coleman MF 

PROVIDER: S-EPMC11161980 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature