细胞自我吞噬在肿瘤发生中的作用－Genes & Development
生物谷报道：最新的Genes & Development杂志上，Eileen White博士与来自Rutgers大学、University of Medicine and Dentistry of New Jersey大学、新泽西癌症研究所的研究人员首次报道，细胞自我吞噬作用能够保护基因组的完整性。为研究自我吞噬看似矛盾的两个作用：细胞生存途径和肿瘤抑制途径提供了新的参考。
White博士利用遗传工程方法得到缺少一个关键自我吞噬基因拷贝的细胞，证实尽管丢失自我吞噬能力，降低了饥饿时肿瘤细胞的存活率，并发的基因组不稳定性能够加速行肿瘤行进。因此，不仅要维持自我吞噬的正常功能，而且要在饥饿时期通过限制基因组损伤保护细胞。White博士说：“弄清肿瘤细胞对代谢压力的反应机制，是设计治疗方法的关键：已经确定的肿瘤中，自我吞噬抑制剂也许促进饥饿的肿瘤细胞死亡，通过预防基因组损伤，利用自我吞噬促进物抑制发生初期和行进过程中的肿瘤。”
原始出处：
Published online before print May 17, 2007
Genes and Development, DOI: 10.1101/gad.1545107
Autophagy suppresses tumor progression by limiting chromosomal instability
Robin Mathew1,2, Sameera Kongara2,3, Brian Beaudoin2,3, Cristina M. Karp2, Kevin Bray2,3, Kurt Degenhardt2,3, Guanghua Chen2, Shengkan Jin4,5, and Eileen White1,2,3,5,6
1 University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA; 2 Center for Advanced Biotechnology and Medicine, Rutgers University Piscataway, New Jersey 08854, USA; 3 Department of Molecular Biology and Biochemistry, Rutgers University Piscataway, New Jersey 08854, USA; 4 Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA; 5 The Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA
Autophagy is a bulk degradation process that promotes survival under metabolic stress, but it can also be a means of cell death if executed to completion. Monoallelic loss of the essential autophagy gene beclin1 causes susceptibility to metabolic stress, but also promotes tumorigenesis. This raises the paradox that the loss of a survival pathway enhances tumor growth, where the exact mechanism is not known. Here, we show that compromised autophagy promoted chromosome instability. Failure to sustain metabolism through autophagy was associated with increased DNA damage, gene amplification, and aneuploidy, and this genomic instability may promote tumorigenesis. Thus, autophagy maintains metabolism and survival during metabolic stress that serves to protect the genome, providing an explanation for how the loss of a survival pathway leads to tumor progression. Identification of this novel role of autophagy may be important for rational chemotherapy and therapeutic exploitation of autophagy inducers as potential chemopreventive agents.
[Keywords: Autophagy; beclin1; genomic instability; apoptosis; cancer]
Received February 23, 2007; revised version accepted April 12, 2007.
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