Kato Yasumasa, Maeda Toyonobu, Suzuki Atsuko, Baba Yuh
Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, 31-1 Misumido, Tomita-machi, Koriyama 963-8611, Japan.
Department of General Clinical Medicine, Ohu University School of Dentistry, 31-1 Misumido, Tomita-machi, Koriyama 963-8611, Japan.
Jpn Dent Sci Rev. 2018 Feb;54(1):8-21. doi: 10.1016/j.jdsr.2017.08.003. Epub 2017 Sep 29.
Initial studies of cancer metabolism in the early 1920s found that cancer cells were phenotypically characterized by aerobic glycolysis, in that these cells favor glucose uptake and lactate production, even in the presence of oxygen. This property, called the Warburg effect, is considered a hallmark of cancer. The mechanism by which these cells acquire aerobic glycolysis has been uncovered. Acidic extracellular fluid, secreted by cancer cells, induces a malignant phenotype, including invasion and metastasis. Cancer cells survival depends on a critical balance of redox status, which is regulated by amino acid metabolism. Glutamine is extremely important for oxidative phosphorylation and redox regulation. Cells highly dependent on glutamine and that cannot survive with glutamine are called glutamine-addicted cells. Metabolic reprogramming has been observed in cancer stem cells, which have the property of self-renewal and are resistant to chemotherapy and radiotherapy. These findings suggest that studies of cancer metabolism can reveal methods of preventing cancer recurrence and metastasis.
20世纪20年代初对癌症代谢的初步研究发现，癌细胞在表型上的特征是有氧糖酵解，即这些细胞即使在有氧的情况下也倾向于摄取葡萄糖并产生乳酸。这种特性被称为瓦伯格效应，被认为是癌症的一个标志。这些细胞获得有氧糖酵解的机制已经被揭示。癌细胞分泌的酸性细胞外液会诱导包括侵袭和转移在内的恶性表型。癌细胞的存活取决于氧化还原状态的关键平衡，而氧化还原状态由氨基酸代谢调节。谷氨酰胺对氧化磷酸化和氧化还原调节极为重要。高度依赖谷氨酰胺且没有谷氨酰胺就无法存活的细胞被称为谷氨酰胺成瘾细胞。在具有自我更新特性且对化疗和放疗有抗性的癌症干细胞中也观察到了代谢重编程。这些发现表明，对癌症代谢的研究可以揭示预防癌症复发和转移的方法。
