Jonckheere Nicolas, Vincent Audrey, Van Seuningen Isabelle
Inserm, UMR837, Team #5 "Mucins, epithelial differentiation and carcinogenesis", Jean-Pierre-Aubert Research Center, rue Polonovski, 59045 Lille cedex, France; Université Lille-Nord de France, 1, place de Verdun, 59045 Lille cedex, France; Centre hospitalier régional et universitaire de Lille, place de Verdun, 59037 Lille cedex, France.
Inserm, UMR837, Team #5 "Mucins, epithelial differentiation and carcinogenesis", Jean-Pierre-Aubert Research Center, rue Polonovski, 59045 Lille cedex, France; Université Lille-Nord de France, 1, place de Verdun, 59045 Lille cedex, France; Centre hospitalier régional et universitaire de Lille, place de Verdun, 59037 Lille cedex, France.
Clin Res Hepatol Gastroenterol. 2014 Sep;38(4):423-5. doi: 10.1016/j.clinre.2014.04.009. Epub 2014 Jun 14.
Autophagy is a lysosomal recycling process essential for tissue or cell homeostasis. The role of autophagy in cancer is complex with either tumor suppressive or pro-carcinogenetic activities. This question has been addressed by Kevin Ryan's laboratory by using Kras-driven genetic engineering mouse models in order to decipher the involvement of essential Atg5/7 autophagy genes and p53 status in pancreatic homeostasis and carcinogenetic progression. The authors show that combined loss of autophagy and p53 dramatically promotes progression from early Pancreatic Intraepithelial Neoplasia (PanIN) lesions towards adenocarcinoma and alters the cellular metabolism with an enrichment of anabolic pathway that can fuel the tumor growth.
自噬是一种对组织或细胞内稳态至关重要的溶酶体循环过程。自噬在癌症中的作用复杂，具有肿瘤抑制或促癌活性。凯文·瑞安实验室通过使用Kras驱动的基因工程小鼠模型来解决这个问题，以阐明必需的Atg5/7自噬基因和p53状态在胰腺内稳态和致癌进展中的作用。作者表明，自噬和p53的联合缺失显著促进了从早期胰腺上皮内瘤变（PanIN）病变向腺癌的进展，并改变了细胞代谢，使合成代谢途径富集，从而为肿瘤生长提供能量。
