Figure 1

Schematic representation of the nuclear reprogramming process from somatic cells, including primary cancer cells. The initial stage of reprogramming includes the induction of somatic cells to pre-induced pluripotent stem cells (Pre-iPSCs) by exogenous pluripotent factors (such as Yamanaka 4 factors) via reprogramming-induced senescence (RIS; which results from DNA damage and metabolic stresses), which results in expression of tumor suppressor genes (such as p21^CIP1 and p16^INK4a) via the activation of p53. The subsequent process is triggered to overcome the barrier of RIS, cell apoptosis, or cell-cycle arrest by shutting off the function of tumor suppressor genes such as p16^INK4a, p21^CIP1, and p53, and then inducing the full commitment of iPSCs (Full-iPSCs) by endogenous stemness genes, as described in the text. Thus, the reaction oxygen species (ROS) produced by oxidative stress might be critical for the induction of endogenous reprogramming factor genes through at least epigenetic changes or antioxidation reactions [60, 69].