Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis.
Qian SunShuzhan LiYanan WangHaiyong PengXiying ZhangYu ZhengChunjia LiLi LiRongrong ChenXinxin ChenWenjing BaiXiangli JiangLiang LiuFeng WeiBoshi WangYu ZhangHui LiXiubao RenHongbing ZhangPublished in: Cell death and differentiation (2018)
As a hallmark of cancer, the Warburg effect (aerobic glycolysis) confers a selective advantage for the survival and proliferation of cancer cells. Due to frequent aberration of upstream proto-oncogenes and tumor suppressors, hyperactive mammalian/mechanistic target of rapamycin (mTOR) is a potent inducer of the Warburg effect. Here, we report that overexpression of a glycolytic enzyme, phosphoglyceric acid mutase-1 (PGAM1), is critical to oncogenic mTOR-mediated Warburg effect. mTOR stimulated PGAM1 expression through hypoxia-inducible factor 1α-mediated transcriptional activation. Blockage of PGAM1 suppressed mTOR-dependent glycolysis, cell proliferation, and tumorigenesis. PGAM1 expression and mTOR activity were positively correlated in non-small cell lung cancer (NSCLC) tissues and PGAM1 abundance was an adverse predictor for patient survival. PGAM1 is thus a downstream effector of mTOR signaling pathway and mTOR-PGAM1 signaling cascade may contribute to the development of Warburg effect observed in cancer. We consider PGAM1 as a novel prognostic biomarker for NSCLC and a therapeutic target for cancer.
Keyphrases
- cell proliferation
- poor prognosis
- signaling pathway
- papillary thyroid
- small cell lung cancer
- long non coding rna
- pi k akt
- gene expression
- cell cycle
- transcription factor
- emergency department
- squamous cell
- regulatory t cells
- dendritic cells
- binding protein
- microbial community
- oxidative stress
- advanced non small cell lung cancer
- young adults
- heat shock protein
- epidermal growth factor receptor