Figure 3.

A summary flow chart of PTEN pathways in genome maintenance and dysfunction in stress management upon PTEN loss. PTEN maintains genome stability and epigenome architecture by regulating distinct but interrelated signaling pathways, including the canonical lipid phosphatase pathway, multiple protein phosphatase-dependent pathways, and an epigenetic pathway. These pathways run awry upon the loss or inactivation of PTEN, leading to the spontaneous generation of genome stress, dysfunction of multiple checkpoints, and tolerance to exogenous stimuli. More studies are needed to illuminate whether loss-of-PTEN-related stress tolerance may be translatable to resistance of PTEN-deficient tumors to anticancer therapies, and how to overcome it.