Research Perspective Volume 11, Issue 3 pp 1065—1068

Hallmarks of the cancer cell of origin: Comparisons with “energetic” cancer stem cells (e-CSCs)

Figure 1. Hypothesis for how senescent cells can mechanistically become cancer stem cells. Senescent cells undergoing cell cycle arrest mount an anti-oxidant defense, to increase their levels of NADH. In turn, increased NADH levels are known to be sufficient to rescue senescent cells from cell cycle arrest, allowing new cell proliferation, by “re-activating” or “resuscitating” senescent cells. Increased mitochondrial power would then drive elevated ATP production and 3D anchorage-independent growth, fostering the generation and propagation of the cancer cell of origin.