The Calcineurin-NFAT-Angiopoietin 2 signaling axis in lung endothelium is critical for the establishment of lung metastases

ABSTRACT: The pre-metastatic niche is a pre-determined site of metastases, awaiting the influx of tumor cells. Here we demonstrate that the calcineurin-NFAT pathway is activated specifically in lung endothelium prior to the detection of tumor cells that preferentially metastasize to the lung. We previously showed that DSCR-1 functions in a negative feedback loop to attenuate calcineurin signaling. Upregulation of the calcineurin pathway via loss of Dscr-1 leads to a significant increase in lung metastasis due to the increased expression of a newly identified NFAT target, Angiopoietin (Ang)-2. An increase in VEGF levels specifically in the lung versus other organ microenvironments triggers a threshold of calcineurin-NFAT signaling that transactivates Ang2 in lung endothelium. Further, we demonstrate

ORGANISM(S): Homo sapiens

SUBMITTER: Shogo Yamamoto 

PROVIDER: E-GEOD-48841 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress