RESUMO
The catalytic subunit p110δ of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD 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 PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo. In contrast, inhibition of PIK3CD by specific small-interfering RNA or idelalisib dramatically suppressed CRC cell growth, migration and invasion in vitro and tumor growth in vivo. Moreover, PIK3CD overexpression increased AKT activity, nuclear translocation of ß-catenin and T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity and decreased glycogen synthase kinase 3ß (GSK-3ß) activity, whereas PIK3CD inhibition exhibited the opposite effects. Furthermore, PIK3CD-mediated cell growth, migration and invasion were reversed by blockade of AKT signaling or depletion of ß-catenin. In addition, PIK3CD expression in colon cancer tissues positively correlated with ß-catenin abnormal expression, which was an independent predictor for OS of colon cancer patients. Taken together, our findings demonstrate that PIK3CD is an independent prognostic factor in CRC and that PIK3CD induces CRC cell growth, migration and invasion by activating AKT/GSK-3ß/ß-catenin signaling, suggesting that PIK3CD might be a novel prognostic biomarker and a potential therapeutic target for CRC.
Assuntos
Proliferação de Células/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias Colorretais/genética , Glicogênio Sintase Quinase 3 beta/genética , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HT29 , Humanos , Invasividade Neoplásica/patologia , RNA Interferente Pequeno/genética , beta Catenina/genéticaRESUMO
BACKGROUND: Selective neurectomy of the innervating nerves of the gastrocnemius muscle is a popular method employed for calf reduction. However, accidental injury to the untargeted adjacent nerves could happen. This study aims to provide detailed morphometry of the motor branches from the tibial nerve innervating the gastrocnemius muscle, the soleus and the medial sural cutaneous nerve in the popliteal fossa. METHODS: 23 lower legs from female cadavers were dissected to explore the origin, length of and the spatial relationship between the four branches given off from the tibial nerve in the popliteal fossa. RESULTS: Our study showed there were seven origin patterns existing among the four nerve branches; the origin of the branches to the medial and lateral heads of the gastrocnemius muscle was located ranging from -16 mm to 22 mm away from the midpoint of the line between the lateral and medial condyles of the femur; In 95% of the specimens, the location of the origin of the nerve branch to the medial head was proximal to its lateral counterpart. The nerve to the medial head was often given off from the medial aspect or the posteromedial aspect of the tibial nerve, while the other three often from the lateral aspect. CONCLUSIONS: A variety of origin patterns among the nerves to the lateral and medial gastrocnemius muscle, the nerve to the soleus muscle and the sural cutaneous nerve exist, necessitating the formulation of diversifying surgical strategies preoperatively and the meticulous and sequential dissection intra-operatively to ensure the lowest level of accidental injury.