NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene.
NFAT1 and NFAT5 act as pro-invasive and pro-migratory transcription factors in breast carcinoma, contributing to the formation of metastases. We report that NFAT3 is specifically expressed in estrogen receptor alpha positive (ERA+) breast cancer cells. We show that NFAT3 inhibits by itself the invasion capacity of ERA+ 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.
Fougère
M
M
CNRS UMR7212, INSERM U944, Université Paris Diderot, Institut d'Hématologie, Hôpital Saint-Louis, Paris Cedex 10, France.
Gaudineau
B
B
Barbier
J
J
Guaddachi
F
F
Feugeas
J-P
JP
Auboeuf
D
D
Jauliac
S
S
D000199:Actins / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000172:deficiency / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D047628:Estrogen Receptor alpha / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*
D000199:Actins; D000209:Acute-Phase Proteins; D047628:Estrogen Receptor alpha; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D050778:NFATC Transcription Factors; D011518:Proto-Oncogene Proteins