PIK 3 CD induces cell growth and invasion by activating AKT / GSK ‐3β/β‐catenin signaling in colorectal cancer

The catalytic subunit p110δ of phosphoinositide 3‐kinase ( PI 3K) encoded by PIK 3 CD has been implicated in some human solid tumors. However, its roles in colorectal cancer ( CRC ) remain largely unknown. Here we found that PIK 3 CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival ( OS ) of patients with colon cancer. The ectopic overexpression of PIK 3 CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK 3 CD by specific small‐interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK 3 CD overexpression increased AKT activity, nuclear translocation of β‐catenin and T‐cell factor/lymphoid enhancer factor ( TCF / LEF ) transcriptional activity and decreased glycogen synthase kinase 3β ( GSK ‐3β) activity, whereas PIK 3 CD inhibition exhibited the opposite effects. Furthermore, PIK 3 CD ‐mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of β‐catenin. In addition, PIK 3 CD expression in colon cancer tissues positively correlated with β‐catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK 3 CD is an independent prognostic factor in CRC and that PIK 3 CD induces CRC cell growth, migration and invasion by activating AKT / GSK ‐3β/β‐catenin signaling, suggesting that PIK 3 CD might be a novel prognostic biomarker and a potential therapeutic target for CRC .