Unknown

Dataset Information

0

Glycine decarboxylase is a metabolic oncogene critical for tumor initiating cells and tumorigenesis in lung cancer


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

Similar Datasets

2011-10-25 | E-GEOD-33198 | biostudies-arrayexpress
2011-10-26 | GSE33198 | GEO
| S-EPMC8270999 | biostudies-literature
| S-EPMC5992284 | biostudies-literature
| S-EPMC4096909 | biostudies-other
| S-EPMC9583459 | biostudies-literature
| S-ECPF-GEOD-51433 | biostudies-other
| S-EPMC3904607 | biostudies-literature
| S-EPMC4716302 | biostudies-literature
| S-EPMC6528107 | biostudies-literature