We found that RB-mediated G2/M phase arrest inhibited GBM cell proliferation by activating the MAPK/ERK pathway, which altered p21/CDC25C/CDK1/Cyclin B protein expression, and RB inhibited GBM invasion by increasing intercellular Ca2+ to suppress the Src/FAK/Paxillin focal adhesion pathway. Here, SRC is linked to glioblastoma.