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English: Mechanisms of PTEN-mediated control of cancer stem cells (CSCs) hallmarks. PTEN deficiency promotes self-renewal through inhibitory phosphorylation of FoxO3a and GSK3β, which increases nuclear β-catenin localization. Furthermore, it induces STAT3 activation by NFkB-mediated IL6 transcription and CXCR4 expression. MicroRNAs (miR-10b, miR-21, miR-106b and TGFβ-induced miR-216a) and PRMT5-mediated methylation are also involved in the downregulation of PTEN and regulation of self-renewal. Hyperactive AKT acts on cell cycle stimulating proliferation trough PAX7, cyclinD1 or C-MYC. PTEN loss may trigger G0 cell cycle arrest and quiescence of CSCs. Activation of mTOR is required for CSC survival and can be associated with the activation of collateral pro-survival pathways such as HIF-1α. S100A4 and BMI, along with several miRNAs (miR-20a/miR-200c, miR-17, miR-221/222) impair PTEN function, thus promoting EMT and metastatic progression. The lncRNA-GAEA inhibits PTEN lipid phosphatase activity, switching on its protein phosphatase activity and promoting the accumulation of EMT master regulators such as TWIST, SNAIL, and YAP. Moreover, activation of the RAS/MAPK pathway, NOTCH1 signaling, and MAOA cooperate with PTEN/PI3K/AKT axis to promote the EMT program.^[1]