Aberrant cellular plasticity (“dys-plasticity”) could occur in vivo, which contributes significantly to disease development, especially in cancer. Recently, we showed p27-/- cells are dysplastic due to the derepression of Sox2, an essential pluripotency gene. More importantly this dys-plasticity plays a causal role in p27 dependent tumorigenesis and developmental defects. However, how the dys-plasticity is induced and how does it contribute to tumorigenesis remains largely unknown. To address these questions, we focus on understanding the regulation of Sox2. More precisely, we investigate how Sox2 is repressed in somatic cells and how activation of Sox2 contributes to oncogenic reprogramming.