Fig. 1

Model of RUNX2 and PI3K/AKT reciprocal interaction as a driving force for tumor progression. a. AKT activity results in up regulation of RUNX2 mRNA, stabilization of RUNX2 protein or activation of RUNX2 transcriptional activity. b. RUNX2 transcriptional activity leads to higher expression of the PI3K subunits p110β and p85, AKT or mTOR and RICTOR, two major components of the mTORC2 complex. c. Mutual activation of AKT and RUNX2 in the context of cancer cells might favor tumor progression. A pioneering study [47] shows that RUNX2 and the PI3K/AKT axis are mutually dependent on each other in the regulation of osteoblast and chondrocyte differentiation and their migration. We propose that a similar feed-forward loop could operate in tumor cells to potentiate RUNX2 and PI3K/AKT activities and generate the pro-migratory and pro-invasive behavior of tumor cells. Studies described in paragraphs 1 and 2 support this hypothesis