Peter W and colleagues investigated whether NEDD4 expression was associated with the PTEN mutation status in 114 CRC cases, and revealed that NEDD4 knockdown would not affect PTEN protein levels or the PI3K/AKT signaling pathway, indicating that the regulation of PTEN by NEDD4 is not stable and NEDD4 can independently drive CRC development without regulating PTEN levels [59]. The gene discussed is AKT1; the disease is colorectal carcinoma.