Hypothetical representation of opposite downstream effects of two signaling pathways on the G1 phase of the cell cycle in a breast tumor-initiating cell. During the early G1 subphase the cell integrates signals that may lead it to several fates (differentiation, apoptosis, senescence, quiescence, pause for DNA repair, progression to S phase) . Inhibition of the JUN/MAPK pathway shortens the early G1 subphase rendering the cell independent of differentiation and apoptotic factors. In the same time, activation of the PI3K/AKT pathway induces the cell to progress to late G1 subphase beyond the restriction (R) point; the cell may then undergo symmetric (proliferation) or asymmetric (self-renewal) division. In green: proteins with repressive effect, in red: proteins with activating effect.