Corcelle Elisabeth A, Puustinen Pietri, Jäättelä Marja
Apoptosis Department and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
FEBS J. 2009 Nov;276(21):6084-96. doi: 10.1111/j.1742-4658.2009.07332.x. Epub 2009 Sep 29.
Macroautophagy (hereafter referred to as autophagy) is a tightly regulated lysosome-dependent catabolic pathway. During this process, cytosolic constituents are sequestered into autophagosomes, which subsequently fuse with lysosomes to become autolysosomes, where their contents are degraded. Autophagy contributes to the maintenance of the cellular energy homeostasis, to the clearance of damaged organelles and to adaptation to environmental stresses. Accordingly, autophagy defects have been linked to a wide range of human pathologies, including cancer. The recent discovery of several evolutionarily conserved genes involved in autophagosome formation has greatly stimulated the autophagy research, and the complex signalling networks regulating mammalian autophagy have begun to emerge. Here, we draw the current picture of signalling pathways connecting mitogenic and stress-induced signals to the initiation and maturation of autophagosomes and discuss the possibilities of their targeting as therapeutic adjuvants in anticancer therapy.
巨自噬(以下简称自噬)是一种受到严格调控的、依赖溶酶体的分解代谢途径。在此过程中,胞质成分被隔离到自噬体中,自噬体随后与溶酶体融合形成自溶酶体,其内容物在自溶酶体中被降解。自噬有助于维持细胞能量稳态、清除受损细胞器以及适应环境应激。因此,自噬缺陷与包括癌症在内的多种人类疾病相关联。最近发现了几个参与自噬体形成的进化保守基因,这极大地推动了自噬研究,并且调控哺乳动物自噬的复杂信号网络已开始显现。在此,我们描绘了将有丝分裂原和应激诱导信号与自噬体的起始和成熟联系起来的信号通路的当前情况,并讨论了将其作为抗癌治疗中的治疗佐剂进行靶向治疗的可能性。