Fig. 7

MiR-16 affects the pro-tumorigenic properties of the fibroblasts by controlling the levels of HGF in an FGFR-1- and MEK1-dependent fashion. According to our data, miR-16 reduces fibroblast HGF secretion by direct targeting of HGF itself and by inhibiting the FGFR-1 pathway, which in turn promotes HGF expression. In fact, even if not directly targeting the FGFR-1 mRNA, miR-16 reduces FGFR-1 protein levels and directly targets MEK1, which is crucial for FGFR-1 downstream signaling. Moreover, HGF seems to contribute to FGFR-1 expression. When miR-16 is reduced or lost, HGF is secreted by fibroblasts and contributes to cancer cell aggressiveness through the stimulation of cMet pathway. This activation results in increased proliferation and motility of the cancer cells. Interestingly, the presence of HGF seems to favor the increased levels of FGFR-1 supporting the idea that a cross-talk exists between cMet and FGFR-1 receptors