PTEN and neoplasm: The cytoplasmic PTEN exerts tumor suppressive effect mainly by antagonizing the PI3K-AKT-dependent cell growth and survival, whereas the nuclear PTEN suppresses tumor by multiple mechanisms independent of PI3K-AKT, including stabilizing another tumor suppressor TP53 by interacting with p53, inhibiting cyclin D1 expression, inducing the expression of RAD51 and thus enhancing DNA repair, and promoting ubiquitin-dependent degradation of oncoproteins such as Polo-like kinase 1 and aurora kinase AURK (Chen et al., 2018, Milella et al., 2015).