Figure 4.

Cancer cells have different thresholds for PP2A activity than normal cells Normal cells (left) maintain median PP2A activity levels and have a larger tolerance for fluctuations in PP2A phosphatase activity. In contrast, malignant cells (right) become addicted to low levels of PP2A activity and, therefore, become more susceptible to fluctuations in activity. Upon therapeutic activation of PP2A, malignant cells cannot withstand PP2A activation returning to baseline levels and the subsequent loss of oncogenic signaling. Similarly, given that malignant cells already function on low levels of PP2A activity, inhibition of PP2A activity results in a loss of survival signals and cell apoptosis. Since PP2A activators and inhibitors display little to no toxicity, this would suggest that normal cells are able to maintain the signals necessary for survival in both contexts.