LKB1-AMPK信号通路：肿瘤抑制中的代谢与生长调控
The LKB1-AMPK pathway: metabolism and growth control in tumour suppression.
作者信息
Shackelford David B, Shaw Reuben J
机构信息
Dulbecco Center for Cancer Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
出版信息
Nat Rev Cancer. 2009 Aug;9(8):563-75. doi: 10.1038/nrc2676.
Abstract
In the past decade, studies of the human tumour suppressor LKB1 have uncovered a novel signalling pathway that links cell metabolism to growth control and cell polarity. LKB1 encodes a serine-threonine kinase that directly phosphorylates and activates AMPK, a central metabolic sensor. AMPK regulates lipid, cholesterol and glucose metabolism in specialized metabolic tissues, such as liver, muscle and adipose tissue. This function has made AMPK a key therapeutic target in patients with diabetes. The connection of AMPK with several tumour suppressors suggests that therapeutic manipulation of this pathway using established diabetes drugs warrants further investigation in patients with cancer.
摘要
在过去十年中，对人类肿瘤抑制因子LKB1的研究揭示了一条将细胞代谢与生长控制及细胞极性联系起来的新信号通路。LKB1编码一种丝氨酸 - 苏氨酸激酶，该激酶直接磷酸化并激活AMPK（一种核心代谢传感器）。AMPK调节肝脏、肌肉和脂肪组织等特殊代谢组织中的脂质、胆固醇和葡萄糖代谢。这一功能使AMPK成为糖尿病患者的关键治疗靶点。AMPK与多种肿瘤抑制因子的关联表明，使用已有的糖尿病药物对该通路进行治疗性调控，在癌症患者中值得进一步研究。
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