Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism

gandanxiaoyang

生物通报道 4 i5 z7 K5 x) X" \, K7 U9 p, m
行为就像贪食的怪物，肿瘤需要供给充足的细胞构件例如氨基酸和核苷酸来确保在恶劣的生存环境下保持快速地生长。然而科学家们对于肿瘤如何满足这些迅速生长的要求还没获得充分地理解。现在来自加州理工学院(Caltech)的化学家们首次证实一种称作GlcNAc ("glick-nack")的特殊糖类，在维持癌性怪物的“喂养”中发挥了关键性作用。这一研究发现为癌症的治疗干预提供了新的潜在靶点。新的研究结果发表在本周出版的《科学》（Science）杂志上。8 \7 w1 H$ x# z+ m: o& V1 `! N; [
Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism! K  ?( [/ G6 @/ K: J. ^
Cancer cells must satisfy the metabolic demands of rapid cell growth within a continually changing microenvironment. We demonstrated that the dynamic posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a key metabolic regulator of glucose metabolism. O-GlcNAcylation was induced at serine 529 of phosphofructokinase 1 (PFK1) in response to hypoxia. Glycosylation inhibited PFK1 activity and redirected glucose flux through the pentose phosphate pathway, thereby conferring a selective growth advantage on cancer cells. Blocking glycosylation of PFK1 at serine 529 reduced cancer cell proliferation in vitro and impaired tumor formation in vivo. These studies reveal a previously uncharacterized mechanism for the regulation of metabolic pathways in cancer and a possible target for therapeutic intervention.