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)