细胞衰老会引起衰老相关性轻度炎症（senescence-associated para-inflammation）。这种炎症反应一方面通过延续生长抑制，清除衰老细胞保持了正常器官组织的稳态，抑制了癌症的发生发展；另一方面炎症反应也为癌细胞带来了支持其生长的巨噬细胞，成纤维细胞并促进癌组织中血管的生成。那么什么是这种炎症反应在这两个不同角色之间转换的关键呢？来自以色列、德国、芬兰、美国的研究者在CKIα基因敲除的小鼠肠组织中找到了答案。在小鼠肠组织中单独缺失或降低CKIα表达量时，会引起衰老相关的轻度炎症反应并且伴随着大肠癌的生长停滞。而当同时缺失p53时，这个炎症反应会失去对癌细胞增殖的控制能力，反而会加快癌细胞的增殖及侵染。文章还阐明了炎症抑制性非固醇类抗癌药物的可能机制。（生物谷 Bioon.com）
生物谷推荐的英文内容
Cell Cancer Cell Doi: 10.1016/j.ccr.2013.06.005
A Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism
Ariel Pribluda, Ela Elyada, Zoltan Wiener, Haya Hamza, Robert E. Goldstein, Moshe Biton, Ido Burstain,Yael Morgenstern, Guy Brachya, Hana Billauer, Sharon Biton, Irit Snir-Alkalay, Domagoj Vucic, Katharina Schlereth,Marco Mernberger, Thorsten Stiewe, Moshe Oren, Kari Alitalo, Eli Pikarsky and Yinon Ben-Neriah
Senescence, perceived as a cancer barrier, is paradoxically associated with inflammation, which promotes tumorigenesis. Here, we characterize a distinct low-grade inflammatory process in stressed epithelium that is related to para-inflammation; this process either represses or promotes tumorigenesis, depending on p53 activity. Csnk1a1 (CKIα) downregulation induces a senescence-associated inflammatory response (SIR) with growth arrest in colorectal tumors, which loses its growth control capacity in the absence of p53 and instead, accelerates growth and invasiveness. Corresponding processes occur in CKIα-deleted intestinal organoids, assuming tumorigenic transformation properties ex vivo, upon p53 loss. Treatment of organoids and mice with anti-inflammatory agents suppresses the SIR and prevents p53-deficient organoid transformation and mouse carcinogenesis. SIR/para-inflammation suppression may therefore constitute a key mechanism in the anticarcinogenic effects of nonsteroidal anti-inflammatory drugs.
