Fantin Valeria R, St-Pierre Julie, Leder Philip
Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
Cancer Cell. 2006 Jun;9(6):425-34. doi: 10.1016/j.ccr.2006.04.023.
Alterations in cellular metabolism are among the most consistent hallmarks of cancer. Herein we have investigated the relationship between increased aerobic lactate production and mitochondrial physiology in tumor cells. To diminish the ability of malignant cells to metabolize pyruvate to lactate, lactate dehydrogenase A (LDH-A) levels were knocked down by means of LDH-A short hairpin RNAs. Reduction in LDH-A activity resulted in stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential. It also compromised the ability of these tumor cells to proliferate under hypoxia. The tumorigenicity of the LDH-A-deficient cells was severely diminished, and this phenotype was reversed by complementation with the human ortholog LDH-A protein. These results demonstrate that LDH-A plays a key role in tumor maintenance.
细胞代谢改变是癌症最一致的特征之一。在此，我们研究了肿瘤细胞中需氧乳酸生成增加与线粒体生理学之间的关系。为了降低恶性细胞将丙酮酸代谢为乳酸的能力，通过乳酸脱氢酶A（LDH-A）短发夹RNA敲低LDH-A水平。LDH-A活性的降低导致线粒体呼吸的刺激和线粒体膜电位的降低。这也损害了这些肿瘤细胞在缺氧条件下增殖的能力。LDH-A缺陷细胞的致瘤性严重降低，并且通过与人同源LDH-A蛋白互补可逆转该表型。这些结果表明，LDH-A在肿瘤维持中起关键作用。
