NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene

Abstract

NFAT1 and NFAT5 act as pro-invasive and promigratory transcription factors in breast carcinoma, contributing to the formation of metastases. We report that NFAT3 is specifically expressed in estrogen receptor a positive (ERA þ ) breast cancer cells. We show that NFAT3 inhibits by itself the invasion capacity of ERA þ breast cancer cells and needs to cooperate with ERA to inhibit their migration. Conversely, NFAT3 downregulation results in actin reorganization associated with increased migration and invasion capabilities. NFAT3 signaling reduces migration through inhibition of Lipocalin 2 (LCN2) gene expression. Collectively, our study unravels an earlier unknown NFAT3/LCN2 axis that critically controls motility in breast cancer.

Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor

“…S100A4 or metastasin, which is a member of the S100 family of calcium-binding proteins, has been shown to have an important role in breast cancer progression (Helfman et al, 2005;Garrett Regulation of NFAT5 by ddx5/ddx17 S Germann et al et al, 2006). We have recently reported that lipocalin 2 (LCN2), which also plays a role in breast cancer progression (Yang et al, 2009;Leng et al, 2011), is regulated by NFAT transcriptional factors (Fougere et al, 2010). As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels ( Figure 3a).…”

“…It is now well documented that NFAT proteins are also present in non-immune cells and regulate a variety of signaling pathways involved in cell growth and development (Baksh et al, 2002;Chuvpilo et al, 2002;Mancini and Toker, 2009;Muller and Rao, 2010). Importantly, members of the NFAT family, in particular NFAT5, have recently been involved in the migratory capacity of breast cancer cells (Jauliac et al, 2002;Ayers et al, 2004;Yoeli-Lerner et al, 2005;Mancini and Toker, 2009;Fougere et al, 2010;Muller and Rao, 2010).…”

Adipokines – Toward the Molecular Dissection of Interactions Between Stromal Adipocytes and Breast Cancer Cells

“…The lung metastasis could be blocked by injection of a polyclonal antibody against lipocalin-2 ( Leng et al 2009). In HER2-positive human breast cancer cell line SKBR3, knocking down lipocalin-2 expression reduced the migration and in and ER-positive MCF-7 cells, These findings are consistent with the study by Fougere et al suggesting that the anti-migration activity of NFAT3 is through inhibition of lipocalin-2 gene expression (Fougere et al 2010). In human tissue and urine samples, lipocalin-2 levels are consistently associated with invasive breast cancer ).…”

Inhibition of Breast Cancer Metastasis Via PITPNM3 by Pachymic Acid

“…Breast cancer survival rate falls from about 90% to 20% for metastatic diseases (Fougere et al, 2010;Wang et al, 2011). In the process of metastasis, it is vital for tumor cell to arrest in mediums, regulated by series of stimulus or inhibitors in the microenvironment.…”