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自噬与癌症:肿瘤细胞和组织代谢的动态变化

Autophagy and cancer: dynamism of the metabolism of tumor cells and tissues.

作者信息

Tsuchihara Katsuya, Fujii Satoshi, Esumi Hiroyasu

机构信息

Cancer Physiology Project, Research Center for Innovative oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.

Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.

出版信息

Cancer Lett. 2009 Jun 18;278(2):130-138. doi: 10.1016/j.canlet.2008.09.040. Epub 2008 Nov 11.

Abstract

Autophagy is a dynamic process involving the bulk degradation of cytoplasmic organelles and proteins. Based on the function of "cellular recycling", autophagy plays key roles in the quality control of cellular components as well as supplying nutrients and materials for newly constructed structures in cells under metabolic stresses. The physiological relevance of autophagy in tumor formation and progression is still controversial. The cytoprotective function of autophagy in cells subjected to starvation might enhance the prolonged survival of tumor cells that are often exposed to metabolic stresses in vivo. Meanwhile, a tumor-suppressive function of autophagy has also been suggested. Autophagy-related cell death has been regarded as a primary mechanism for tumor suppression. In addition, the loss of autophagy induced genome instability and significant necrosis with inflammation in transplanted mouse tumor models, suggesting an additional function of autophagy in the suppression of tumor formation and growth. Until now, investigations supporting and proving the above possibilities have not been fully completed using clinical samples and equivalent animal models. Though monitoring and the interpretation of autophagy dynamism in tumor tissues are still technically difficult, identifying the autophagic activity in clinical samples might be necessary to clarify the pathophysiological relevance of autophagy in tumor formation and progression as well as to develop new therapeutic strategies based on the regulation of autophagy.

摘要

自噬是一个动态过程,涉及细胞质细胞器和蛋白质的大量降解。基于“细胞循环利用”功能,自噬在细胞成分的质量控制中发挥关键作用,同时在代谢应激下为细胞中新构建的结构提供营养和物质。自噬在肿瘤形成和进展中的生理相关性仍存在争议。自噬在饥饿细胞中的细胞保护功能可能会增强体内经常遭受代谢应激的肿瘤细胞的长期存活能力。与此同时,也有人提出自噬具有肿瘤抑制功能。自噬相关的细胞死亡被认为是肿瘤抑制的主要机制。此外,在移植小鼠肿瘤模型中,自噬缺失会导致基因组不稳定和伴有炎症的显著坏死,这表明自噬在抑制肿瘤形成和生长方面还有其他功能。到目前为止,使用临床样本和等效动物模型对上述可能性进行支持和验证的研究尚未完全完成。尽管监测和解释肿瘤组织中的自噬动态变化在技术上仍然困难,但识别临床样本中的自噬活性可能对于阐明自噬在肿瘤形成和进展中的病理生理相关性以及基于自噬调节开发新的治疗策略是必要的。

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