MAPK pathway
Mitogen-activated protein kinases (MAPK) play key roles in many cellular programs, including cell proliferation, differentiation, motility and survival [64], and studies have indicated they may influence the OSC phenotype: MAPK signaling has been linked to cytoskeletal rearrangement during tumoral invasion in osteosarcoma cells; and the ERK/MAPK pathway has been associated with differentially expressed proteins involved in the enhanced invasiveness and motility of OSCs [18]. ERK activation of TNFα and IL-1 was implicated in maintaining AX cells, a OSC cell line, in an undifferentiated state, thereby promoting tumor progression and reducing osteoblastic gene expression [40].