Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Autophagy. 2012 Feb 1;8(2):273-4. doi: 10.4161/auto.8.2.18941.
Autophagy is a fundamental salvage pathway that encapsulates damaged cellular components and delivers them to the lysosome for degradation and recycling. This pathway usually conducts a protective cellular response to nutrient deprivation and various stresses. Tumor cells live with metabolic stress and use autophagy for their survival during tumor progression and metastasis. Genomic instability in tumor cells may result in amplification of crucial gene(s) for autophagy and upregulate the autophagic pathway. We demonstrate that a cancer-associated gene, LAPTM4B, plays an important role in lysosomal functions and is critical for autophagic maturation. Its amplification and overexpression promote autophagy, which renders tumor cells resistant to metabolic and genotoxic stress and results in more rapid tumor growth.
自噬是一种基本的回收途径，它可以包裹受损的细胞成分，并将其递送至溶酶体进行降解和再循环。这条途径通常会对营养缺乏和各种应激做出保护性的细胞反应。肿瘤细胞在代谢应激下生存，并在肿瘤进展和转移过程中利用自噬作用。肿瘤细胞的基因组不稳定性可能导致自噬关键基因的扩增，并上调自噬途径。我们证明了一个癌相关基因 LAPTM4B 在溶酶体功能中发挥重要作用，并且对于自噬的成熟至关重要。其扩增和过表达促进自噬，使肿瘤细胞对代谢和遗传毒性应激具有抗性，并导致更快的肿瘤生长。
