Most importantly, for the first time, we have discovered a novel reverse regulation within the traditional PTEN/AKT signaling pathway, whereby AKT induces GATA2 with consequent decreased PTEN transcription, likely germane in tumor invasion and metastases but not initiation.
Meanwhile, CCR7 functioned as a positive upstream factor of the AKT pathway contributing to the expression of GATA2, promoting trophoblast migration, and invasion via MMP2.
Furthermore, GATA2 gene silencing in human prostate cancer LNCaP cells led to a marked reduction in cell migration, tissue invasion, focal adhesion disassembly and to a dramatic change in cell transcriptomes, indicating that GATA2 plays a critical role in prostate cancer metastasis.
Ectopic expression of GATA2 or RNAi-mediated knockdown of GATA2 significantly enhanced or inhibited proliferation, migration and invasion of glioma cells.