Glycine decarboxylase is a metabolic oncogene critical for tumor initiating cells and tumorigenesis in lung cancer
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ABSTRACT: New approaches to cancer therapies could benefit from a better understanding of the molecular determinants critical to tumor initiating cells (TICs). Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). From a broad range of primary NSCLC tumors, we isolated CD166+ lung TICs that consistently initiated tumorigenesis in NOD/SCID Il2rγ-/- mice. Lung TICs express high levels of the oncogenic stem cell factor LIN28B and the metabolic enzyme GLDC. Over-expression of GLDC and other glycine/serine metabolism enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. Metabolomic analysis found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. Clinically, GLDC over-expression, observed in multiple cancer types, predicts poorer survival in lung cancer patients. Our findings establish a novel link between glycine metabolism and tumorigenesis, and provide novel targets for advancing anti-cancer therapy. Total RNA obtained from tumor sphere compared to CD166+ and CD166- selected cells of xenograft, primary tumor and normal donors
ORGANISM(S): Homo sapiens
SUBMITTER: Yang Henry
PROVIDER: S-ECPF-GEOD-33198 | biostudies-other |
REPOSITORIES: biostudies-other
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