Activation of multiple signal transduction pathways by niche-driving oncogenes. Niche-driving oncogenes activate key signal transduction pathways at multiple levels, including the cell membrane, cytoplasm, and nucleus. The oncogenes activate transcriptome and secretome in cancer cells and initiate a tumor microenvironment (TME) with distinct features, including cancer aerobic metabolism, cancer stem cell niche, tumor neovascularization, tumor-associated macrophages, cancer-associated stromal cells, and derived niche factors. (, niche-driving oncogenes; , normal signaling proteins; , key signal pathways; , normal proteins that regulate cell proliferation or apoptosis; , promotion of signal transduction; , inhibition of signal transduction; and , mutated growth factors activating proto-oncogenes)