A Senescence-Inflammatory Switch from Cancer-Inhibitory to Cancer-Promoting Mechanism

作者：Pribluda Ariel; Elyada Ela; Wiener Zoltan; Hamza Haya; Goldstein Robert E; Biton Moshe; Burstain Ido; Morgenstern Yael; Brachya Guy; Billauer Hana; Biton Sharon; Snir Alkalay Irit; Vucic Domagoj; Schlereth Katharina; Mernberger Marco; Stiewe Thorsten; Oren Moshe; Alitalo Kari; Pikarsky Eli; Ben Neriah Yinon^*

来源：Cancer Cell, 2013, 24(2): 242-256.

DOI：10.1016/j.ccr.2013.06.005

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 (CKI alpha) 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 CKI alpha-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.

• 出版日期2013-8-12
• 单位河北医科大学