Pancreatic ductal adenocarcinoma （PDAC） represents a biggest challenge in clinic oncology due to its invasiveness and lack of tar- geted therapeutics. Our recent study showed that schizophrenia susceptibility factor...Pancreatic ductal adenocarcinoma （PDAC） represents a biggest challenge in clinic oncology due to its invasiveness and lack of tar- geted therapeutics. Our recent study showed that schizophrenia susceptibility factor dysbindin exhibited significant higher level in serum of PDAC patients. However, the functional relevance of dysbindin in PDAC is still unclear. Here, we show that dysbindin pro- motes tumor growth both in vitro and in vivo by accelerating the G1/S phase transition in cell cycle via PI3K/AKT signaling path- way. Mechanistically, dysbindin interacts with PI3K and stimulates the kinase activity of PI3K. Moreover, overexpression of dysbindin in PDAC is correlated with clinicopathological characteristics significantly, such as histological differentiation （P = 0.011） and tumor size （P = 0.007）. Kaplan-Meier survival curves show that patients with high dysbindin expression exhibit poorer overall survival, compared to those with low dysbindin expression （P 〈 0.001）. Multivariate analysis reveals that dysbindin is an independ- ent prognostic factor for pancreatic ductal adenocarcinoma （P = 0.001）. Thus, our findings reveal that dysbindin is a novel PI3K acti- vator and promotes PDAC progression via stimulation of PI3K/AKT. Dysbindin therefore represents a potential target for prognosis and therapy of PDAC.展开更多
文摘Pancreatic ductal adenocarcinoma （PDAC） represents a biggest challenge in clinic oncology due to its invasiveness and lack of tar- geted therapeutics. Our recent study showed that schizophrenia susceptibility factor dysbindin exhibited significant higher level in serum of PDAC patients. However, the functional relevance of dysbindin in PDAC is still unclear. Here, we show that dysbindin pro- motes tumor growth both in vitro and in vivo by accelerating the G1/S phase transition in cell cycle via PI3K/AKT signaling path- way. Mechanistically, dysbindin interacts with PI3K and stimulates the kinase activity of PI3K. Moreover, overexpression of dysbindin in PDAC is correlated with clinicopathological characteristics significantly, such as histological differentiation （P = 0.011） and tumor size （P = 0.007）. Kaplan-Meier survival curves show that patients with high dysbindin expression exhibit poorer overall survival, compared to those with low dysbindin expression （P 〈 0.001）. Multivariate analysis reveals that dysbindin is an independ- ent prognostic factor for pancreatic ductal adenocarcinoma （P = 0.001）. Thus, our findings reveal that dysbindin is a novel PI3K acti- vator and promotes PDAC progression via stimulation of PI3K/AKT. Dysbindin therefore represents a potential target for prognosis and therapy of PDAC.
