Interaction of Nrf2 with dimeric STAT3 induces IL-23 expression: Implications for breast cancer progression. (1st March 2021)

• Record Type: Journal Article
• Authors: Kim, Su-Jung; Saeidi, Soma; Cho, Nam-Chul; Kim, Seung Hyeon; Lee, Han-Byoel; Han, Wonshik; Noh, Dong-Young; Surh, Young-Joon
• Is Part Of: Cancer letters. Volume 500(2021)
• Page Start: 147
• Page End: 160
• Publication Date: 2021-03-01
• Subjects: Nrf2 -- STAT3 -- IL-23A -- Breast cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.11.047
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Persistent activation of STAT3 and Nrf2 is considered to stimulate the aggressive behavior of basal-like breast cancer (BLBC). However, the precise mechanism underlying sustained overactivation of these transcription factors and their roles in breast cancer progression remain elusive. Analysis of the TCGA multi-omics data showed that high levels of STAT3 and Nrf2 mRNA were correlated with elevated expression of P-STAT3 Y705 and Nrf2 target proteins in breast cancer patients. Our present study demonstrates a unique interaction between Nrf2 and STAT3 in the maintenance and progression of BLBC. RNA sequencing analysis identified the gene encoding IL-23A upregulated by concurrent binding of STAT3 and Nrf2 to its promoter. IL-23A depletion also showed the similar phenotypic changes to those caused by double knockdown of both transcription factors. In conclusion, the STAT3-Nrf2 interaction accelerates BLBC growth and progression by augmenting IL-23A expression, which underscores the importance of subtype-specific molecular pathways in human breast cancer. Highlights: Tumors from breast cancer patients exhibit high co-expression of P-STAT3 Y705 and Nrf2. Nrf2 and STAT3 physically interact, and the complex was detected predominantly in nucleus. The Nrf2 and STAT3 complex enhances IL-23A expression by binding to its promoter.