Figure 2.

(A) A schematic of the hybrid model for therapeutic approaches. (Top) Simplified model of the core control system (miR-451 and AMPK complex) in response to various glucose levels at a tumor cell site. The core system determines the cell fate, either proliferation or migration. Chemoattractants in the brain tissue determine the migration direction of the cell. (Bottom, Left) Model domain: some migratory cancer cells (blue) near the tumor core site are activated to become a proliferative one (green) via miR-451-AMPK regulation in response to glucose injection levels (red thunder) at the center of the tumor site. (Bottom, right) changes in the length of the a-axis of a cell (the ellipsoid) under a given force (f_a; arrow) consist of the passive change in the first component (a Maxwell element in parallel with a non-linear spring) and the change due to the growth ($u_a^g$). The growth component depends on the levels of miR-451 and AMPK complex, and the force (f_a). The mechanical and growth elements are the same along all axes. (B) miR-451 activity and levels of its target complex (CAB39/LKB1/AMPK) were represented by “m” and “a,” respectively. (C) The migratory and proliferative regions based on miR-451 activity and AMPK levels.