NFAT AND CELLULAR MOTILITY REGULATION IN BREAST CARCINOMA
NFAT isotypes cellular distribution
We have shown that NFAT transcription factors are expressed and active ind are differentially expressed in breast carcinoma.
We found that RNA of every gene -but NFAT3- are similarly detected independently of the cells' ERalpha (ERA) status. Remarkably, NFAT3 expression at the RNA as well as at the protein level is restricted to ERA+ cells, whereas neither NFAT1 nor NFAT2 proteins are detected in ERA+ cells ; NFAT1 protein is present only in ERA- cells, NFAT2 protein is absent in the ERA- cells, and NFAT5 is found in both type of cells.
Differential regulation of cellular motility by NFAT isotypes
We identifIied that some of members of the NFAT isotypes, NFAT1 and NFAT5, have pro migratory and pro invasive capabilities compared to other members, like NFAT3, that is found in less aggressive ERA+ breast cancer and has anti migratory and anti invasive actions by inhibiting the LCN2 gene transcription in cooperation with other genes targeted by ERA yet to be identified.
Work in progress
We currently work on both the identification of the mechanisms of NFAT transcription factors activation and the identification of their downstream genes required to increase or blunt the cellular motility. The goals of these studies are to be able to provide new therapeutic targets to prevent or cure breast cancer metastases
