期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：34
页码：14542-14546
DOI：10.1073/pnas.0904229106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cancer cells often display defects in mitochondrial respiration, thus the identification of pathways that promote cell survival under this metabolic state may have therapeutic implications. Here, we report that the targeted ablation of mitochondrial respiration markedly increases expression of Polo-like kinase 2 (PLK2) and that it is required for the in vitro growth of these nonrespiring cells. Furthermore, we identify PLK2 as a kinase that phosphorylates Ser-137 of PLK1, which is sufficient to mediate this survival signal. In vivo, knockdown of PLK2 in an isogenic human cell line with a modest defect in mitochondrial respiration eliminates xenograft formation, indicating that PLK2 activity is necessary for growth of cells with compromised respiration. Our findings delineate a mitochondrial dysfunction responsive cell cycle pathway critical for determining cancer cell outcome.
