p53 status determines the role of autophagy in pancreatic tumour development

報告日期: 2014/04/18
報告時間: 5:10/6:00
報告學生: 邱致豪(以英文報告)
講評老師: 賴明德
附件下載: 下載[1398-1396958539-1.pdf] 

p53 status determines the role of autophagy in pancreatic tumour development

Nature. 2013 Dec 12;504(7479):296-300.

Speaker :

邱致豪

Date :

2014.04.18

Commentator :

賴明德老師

Place :

Room 602

Abstract:

Autophagy is an intracellular degradation system. Many papers had demonstrated that autophagy is a complex process that plays a different role in physiology or pathophysiology. Autophagy in cancer has dual roles, as a tumor suppressor that can prevent the accumulation of damaged proteins and organelles, and as a mechanism of cell survival that can promote the growth of established tumors. p53 (a tumor suppressor), which as a transcription factor, that can trigger many anti-proliferative programs by activating or repressing key effector genes. The role of autophagy in tumor development is intrinsically connected to the status of p53. Kras (also called Ki-Ras) is the most common mutational event in pancreatic ductal adenocarcinoma (PDAC). The mice of this paper with pancreases contain an activated oncogenic allele of Kras.The mice also lack the essential autophagy genes Atg5 or Atg7. The results indicate the mice contain oncogenic Kras and lacking p53, and the loss of autophagy, which no longer blocks tumor progression, and accelerates tumor onset. The metabolic analysis reveals the enhanced glucose uptake and enrichment of anabolic pathways, which can fuel tumor growth. These findings provide considerable insight into the role of autophagy in cancer and have important implications for autophagy inhibition in cancer therapy.

Reference:

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Mizushima N. Autophagy: process and function. Genes Dev. 2007 Nov; 21(22):2861-73.