TGF- β1-stimulation of NFATC2 and ATF3 proteins and their interaction for matrix metalloproteinase 13 expression in human breast cancer cells

This study found that TGF-β1 stimulated the expression of the nuclear factor of activated T Cells 2 (NFATC2) in MDA-MB231 cells and provided evidence of its interaction with ATF3. The functional characterization of NFATC2 in association with ATF3 was determined by silencing of NFATC2 using siRNA. Knock-down of NFATC2 decreased the expression of both ATF3 and its target gene MMP13 (matrix metalloproteinase 13, a critical invasive gene) in hBC cells. Chromatin immunoprecipitation revealed that TGF-β1 promoted NFATC2 binding and NFATC2-ATF3 complex binding at the MMP13 promoter region, whereas silencing of NFATC2 decreased their binding in hBC cells. Thus, we uncovered the mechanism of interaction between NFATC2 and ATF3 regulated by TGF-β1, and NFATC2 acted as a pivotal factor in providing ATF3 stability and further drove MMP13 transcription. Targeting NFATC2 and blocking its association with ATF3 could therefore help to slow the progression of breast cancer.PMID:34687766 | DOI:10.1016/j.ijbiomac.2021.10.099
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Source Type: research