文章：

自噬在癌症发展和治疗反应中的作用

The role of autophagy in cancer development and response to therapy

原文发布日期：2005-09-01

DOI: 10.1038/nrc1692

类型: Review Article

开放获取: 否

要点：

1. Autophagy is a process that describes the degradation and recycling of proteins and intracellular components in response to starvation or stress.
2. At the early stage of tumour development, autophagy functions as a tumour suppressor. Expression of beclin 1 (BECN1), a mammalian orthologue of the yeast autophagy-related gene Atg6, reduces tumorigenic capacity through induction of autophagy. Mice that are Becn1^+/− display a remarkable increase in the incidence of lung cancer, hepatocellular carcinoma and lymphoma.
3. At advanced stages of tumour development, autophagy promotes tumour progression. The tumour cells that are located in the central area of the tumour mass undergo autophagy to survive low-oxygen and low-nutrient conditions.
4. Autophagy protects some cancer cells against anticancer treatments by blocking the apoptotic pathway ('protective autophagy'). By contrast, other cancer cells undergo autophagic cell death after cancer therapies.
5. Autophagy is induced mainly through the phosphatidylinositol 3-phosphate kinase (PI3K)–AKT–mTOR (mammalian target of rapamycin) signalling pathway.
6. Manipulation of autophagy has the potential to improve anticancer therapeutics. When tumour cells induce protective autophagy, inhibition of autophagy could sensitize tumour cells to the treatment by activating apoptosis. On the other hand, induction of autophagic cell death can also have a therapeutic value.

要点翻译：

1. 自噬是一种描述在饥饿或应激状态下蛋白质及细胞内组分被降解和回收利用的过程。
2. 在肿瘤发生早期，自噬发挥肿瘤抑制作用。Beclin 1（BECN1）作为酵母自噬相关基因Atg6的哺乳动物同源物，其表达通过诱导自噬降低致瘤能力。Becn1+/-小鼠的肺癌、肝细胞癌和淋巴瘤发病率显著升高。
3. 在肿瘤进展晚期，自噬促进肿瘤发展。位于肿瘤团块中央区域的肿瘤细胞通过自噬在低氧和低营养条件下存活。
4. 自噬通过阻断凋亡途径保护部分癌细胞抵抗抗癌治疗（"保护性自噬"）。相反，其他癌细胞在抗癌治疗后发生自噬性细胞死亡。
5. 自噬主要通过磷脂酰肌醇3-磷酸激酶（PI3K）-AKT-mTOR（雷帕霉素哺乳动物靶蛋白）信号通路诱导。
6. 调控自噬具有改善抗癌治疗的潜力。当肿瘤细胞诱导保护性自噬时，抑制自噬可通过激活凋亡增强肿瘤细胞对治疗的敏感性。另一方面，诱导自噬性细胞死亡也具有治疗价值。

英文摘要：

Autophagy is a process in which subcellular membranes undergo dynamic morphological changes that lead to the degradation of cellular proteins and cytoplasmic organelles. This process is an important cellular response to stress or starvation. Many studies have shed light on the importance of autophagy in cancer, but it is still unclear whether autophagy suppresses tumorigenesis or provides cancer cells with a rescue mechanism under unfavourable conditions. What is the present state of our knowledge about the role of autophagy in cancer development, and in response to therapy? And how can the autophagic process be manipulated to improve anticancer therapeutics?

摘要翻译： 

自噬是一个亚细胞膜发生动态形态变化的过程，这些变化导致细胞蛋白和细胞质细胞器的降解。这一过程是细胞应对压力或饥饿的重要反应。许多研究揭示了自噬在癌症中的重要性，但目前仍不清楚自噬是抑制肿瘤发生，还是在不利条件下为癌细胞提供一种自救机制。关于自噬在癌症发展及治疗反应中的作用，我们目前的认识处于什么状态？又该如何调控自噬过程以提高抗癌治疗效果？

原文链接：

The role of autophagy in cancer development and response to therapy