Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA.
Mol Cell. 2010 Mar 12;37(5):620-32. doi: 10.1016/j.molcel.2010.02.018.
To sustain tumor growth, cancer cells must be able to adapt to fluctuations in energy availability. We have identified a single microRNA that controls glioma cell proliferation, migration, and responsiveness to glucose deprivation. Abundant glucose allows relatively high miR-451 expression, promoting cell growth. In low glucose, miR-451 levels decrease, slowing proliferation but enhancing migration and survival. This allows cells to survive metabolic stress and seek out favorable growth conditions. In glioblastoma patients, elevated miR-451 is associated with shorter survival. The effects of miR-451 are mediated by LKB1, which it represses through targeting its binding partner, CAB39 (MO25 alpha). Overexpression of miR-451 sensitized cells to glucose deprivation, suggesting that its downregulation is necessary for robust activation of LKB1 in response to metabolic stress. Thus, miR-451 is a regulator of the LKB1/AMPK pathway, and this may represent a fundamental mechanism that contributes to cellular adaptation in response to altered energy availability.
为了维持肿瘤生长，癌细胞必须能够适应能量供应的波动。我们已经确定了一种单一的 microRNA，它可以控制神经胶质瘤细胞的增殖、迁移和对葡萄糖剥夺的反应。丰富的葡萄糖允许相对高的 miR-451 表达，促进细胞生长。在低葡萄糖中，miR-451 水平下降，减缓增殖但增强迁移和存活。这使细胞能够在代谢应激中存活并寻找有利的生长条件。在神经胶质瘤患者中，升高的 miR-451 与较短的生存时间相关。miR-451 的作用是通过抑制其结合伙伴 CAB39（MO25 alpha）来介导的 LKB1。miR-451 的过表达使细胞对葡萄糖剥夺敏感，这表明其下调对于 LKB1 在代谢应激下的强烈激活是必要的。因此，miR-451 是 LKB1/AMPK 通路的调节剂，这可能代表了一种基本机制，有助于细胞适应能量供应的改变。
