NFκB and STAT3 synergistically activate the expression of FAT10, a gene counteracting the tumor suppressor p53. Issue 3 (24th January 2014)

• Record Type: Journal Article
• Authors: Choi, Yongwook; Kim, Jong Kyoung; Yoo, Joo-Yeon
• Is Part Of: Molecular oncology. Volume 8:Issue 3(2014:May)
• Page Start: 642
• Page End: 655
• Publication Date: 2014-01-24
• Subjects: STAT3 -- FAT10 -- p53 -- Inflammation -- Tumorigenesis; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1016/j.molonc.2014.01.007
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : Chronic inflammation is one of the main causes of cancer, yet the molecular mechanism underlying this effect is not fully understood. In this study, we identified FAT10 as a potential target gene of STAT3, the expression of which is synergistically induced by NFκB co‐stimulation. STAT3 binding stabilizes NFκB on the FAT10 promoter and leads to maximum induction of FAT10 gene expression. Increased FAT10 represses the transcriptional activity of the tumor suppressor p53, a protein that accelerates the protein degradation of FAT10. This FAT10‐p53 double‐negative regulation is critical in the control of tumorigenesis, as overexpressed FAT10 facilitates the tumor progression in the solid tumor model. In conclusion, transcriptional synergy between STAT3 and NFκB functions to put weight on FAT10 in the mutually inhibitory FAT10‐p53 regulatory loop and thus favors tumorigenesis under inflammatory conditions. Highlights: FAT10, a novel target gene of STAT3, links inflammation and tumorigenesis. STAT3 and NFκB synergistically act for maximum induction of FAT10 expression. FAT10 suppresses transcriptional activity of p53 and accelerates tumorigenesis. Double negative regulatory loop present between tumor suppressor p53 and FAT10.