Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth.

ABSTRACT: Cancer cells often proliferate under hypoxia and reprogram their metabolism. However, how to find targets to effectively block the hypoxia-associated metabolic pathways remains unclear. Here, we developed a tool to conveniently calculate electrons dissipated in metabolic transformations. Based on the law of conservation of electrons in chemical reactions, we further built up an electron balance model for central carbon metabolism, and it can accurately outline metabolic plasticity under hypoxia. Our model specifies that glutamine metabolism reprogrammed for biosynthesis of lipid and/or proline actually acts as the alternative electron bin to enable electron transfer in proliferating cells under hypoxia. Inhibition of both proline biosynthesis and lipogenesis can synergistically suppress ca

SUBMITTER: Liu M 

PROVIDER: S-EPMC7062513 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature