Cancer Research Center, Burnham Institute for Medical Research, 10901 N Torrey Pines Rd, La Jolla, California 92037, USA.
Mol Cell Biol. 2010 Mar;30(6):1303-18. doi: 10.1128/MCB.01101-09. Epub 2010 Jan 25.
p32/gC1qR/C1QBP/HABP1 is a mitochondrial/cell surface protein overexpressed in certain cancer cells. Here we show that knocking down p32 expression in human cancer cells strongly shifts their metabolism from oxidative phosphorylation (OXPHOS) to glycolysis. The p32 knockdown cells exhibited reduced synthesis of the mitochondrial-DNA-encoded OXPHOS polypeptides and were less tumorigenic in vivo. Expression of exogenous p32 in the knockdown cells restored the wild-type cellular phenotype and tumorigenicity. Increased glucose consumption and lactate production, known as the Warburg effect, are almost universal hallmarks of solid tumors and are thought to favor tumor growth. However, here we show that a protein regularly overexpressed in some cancers is capable of promoting OXPHOS. Our results indicate that high levels of glycolysis, in the absence of adequate OXPHOS, may not be as beneficial for tumor growth as generally thought and suggest that tumor cells use p32 to regulate the balance between OXPHOS and glycolysis.
p32/gC1qR/C1QBP/HABP1 是一种在线粒体/细胞表面过度表达的蛋白，在某些癌细胞中过度表达。在这里，我们发现敲低人癌细胞中的 p32 表达会强烈促使其代谢从氧化磷酸化（OXPHOS）向糖酵解转变。p32 敲低细胞表现出线粒体 DNA 编码的 OXPHOS 多肽合成减少，并且在体内的致瘤性降低。在敲低细胞中表达外源性 p32 可恢复野生型细胞表型和致瘤性。众所周知，葡萄糖消耗和乳酸生成的增加，即所谓的“Warburg 效应”，是实体瘤的几乎普遍特征，被认为有利于肿瘤生长。然而，在这里，我们表明，在一些癌症中经常过度表达的一种蛋白能够促进 OXPHOS。我们的结果表明，在没有足够的 OXPHOS 的情况下，高水平的糖酵解可能并不像通常认为的那样有利于肿瘤生长，并表明肿瘤细胞利用 p32 来调节 OXPHOS 和糖酵解之间的平衡。
