Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3.

The success of CD8 T cell-based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and the possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during a pioneer round of mRNA translation (pioneer translation products, or PTPs) are an important source of tumor specific peptides which correlates with the aberrant splicing and transcription events associated with oncogenesis. Here we show that up-regulation of PSME3 proteasome activator in cancer cells results in increased destruction of PTP-derived peptides in the nucleus thus enabling cancer cell to subvert immunosurveillance.

Lipocalin 2, the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion.

NFAT1 is a transcription factor that elicits breast carcinoma cells to become invasive, thus contributing to metastasis. 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.

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

Ddx5 and ddx17 are two highly related RNA helicases involved in both transcription and splicing. These proteins coactivate transcription factors involved in cancer such as the estrogen receptor alpha, p53 and beta-catenin. Ddx5 and ddx17 are part of the splicing machinery and can modulate alternative splicing, the main mechanism increasing the proteome diversity.

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.