ATF4 and neoplasm: The notion of the “supermechano-transcriptional factor” is supported by the observation that when human tumor cells are switched from 2D rigid substrate (modulus of ∼1 GPa, i.e., 1 × 109 Pa) to 3D soft substrate (modulus of ∼100 Pa), many genes and molecules, including ATF4, SLC3A2, CCT3, and hsa-miR-199a-5p, are activated or upregulated to promote stemness and proliferation of tumor-repopulating cells.117