BioProject

NFAT1 is a transcription factor that elicits breast carcinoma cells to become invasive, contributing thus to formation of metastases. More...

NFAT1 is a transcription factor that elicits breast carcinoma cells to become invasive, contributing thus to formation of metastases. The molecular mechanisms by which NFAT1 operates in this respect are still poorly known. Here, we report that NFAT1 increases Lipocalin 2 (LCN2) mRNA and protein expression by binding to specific sites in the LCN2 gene promoter region. We show that the LCN2 protein is required downstream of NFAT1 to increase breast cancer cell invasion. We demonstrate that the NFAT1/LCN2 axis is sufficient to regulate expression of the TNF-like receptor TWEAKR at the RNA level and of its ligand, TWEAK, at the protein level. We show, however, that TWEAKR mediates an anti-invasive effect in breast cancer cells whereas, depending on LCN2 expression, TWEAK has either anti- and pro-invasive capacities. Thus, we identify LCN2 and TWEAKR/TWEAK as critical downstream effectors of NFAT1 to regulate breast cancer cell motility and invasive capacity. Overall design: A six chip study using total RNA recovered from three separate siRNA control transiently transfected cultures of MDA-MB-231 breast cancer cells and three separate siRNA LCN2 transiently transfected cultures of MDA-MB-231 breast cancer cells . Less...