PT  - JOURNAL ARTICLE
AU  - Song, Ruisheng
AU  - Struhl, Kevin
TI  - S100A8/S100A9 cytokine acts as a transcriptional coactivator during breast cellular transformation
AID  - 10.1126/sciadv.abe5357
DP  - 2021 Jan 01
TA  - Science Advances
PG  - eabe5357
VI  - 7
IP  - 1
4099  - http://advances.sciencemag.org/content/7/1/eabe5357.short
4100  - http://advances.sciencemag.org/content/7/1/eabe5357.full
SO  - Sci Adv2021 Jan 01; 7
AB  - Cytokines are extracellular proteins that convey messages between cells by interacting with cognate receptors at the cell surface and triggering signaling pathways that alter gene expression and other phenotypes in an autocrine or paracrine manner. Here, we show that the calcium-dependent cytokines S100A8 and S100A9 are recruited to numerous promoters and enhancers in a model of breast cellular transformation. This recruitment is associated with multiple DNA sequence motifs recognized by DNA binding transcription factors that are linked to transcriptional activation and are important for transformation. The cytokines interact with these transcription factors in nuclear extracts, and they activate transcription when artificially recruited to a target promoter. Nuclear-specific expression of S100A8/A9 promotes oncogenic transcription and leads to enhanced breast transformation phenotype. These results suggest that, in addition to its classical cytokine function, S100A8/A9 can act as a transcriptional coactivator.