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
Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of eryth...Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of erythropoiesis is that following each mitosis the daughter cells are morphologically and functionally different from the parent cell from which they are derived, demonstrating the need to study erythropoiesis in a stage-specific manner. This has been impossible until recently due to lack of methods for isolating erythroid cells at each distinct developmental stage. This review summarizes recent advances in the development of methods for isolating both murine and human erythroid cells and their applications. These methods provide powerful means for studying normal and impaired erythropoiesis associated with hematological disorders.展开更多
Aurora kinases have become a hot topic for research as they have been found to play an important role in various stages of mitotic cell division and to participate in malignant conversions of tumors. The participation...Aurora kinases have become a hot topic for research as they have been found to play an important role in various stages of mitotic cell division and to participate in malignant conversions of tumors. The participation of Aurora kinases in the regulation of oocyte meiosis has been recently reported, but their participation in mammalian early embryonic development remained unclear. The object of our study was to establish the spatio-temporal expression pattern of Aurora kinase B (AURKB) in mouse zygotes during the first cleavage, to reveal its functions in the early development of mouse zygotes, and to define the involvement of AURKB in mitogen-activated protein kinase (MAPK) signaling. Our results showed that in mouse zygotes AURKB expression increased in G1 phase and peaked in M phase. AURKB protein distribution was found to be in association with nuclei and distributed throughout the cytoplasm in a cell cycle-dependent manner. Functional disruption of AURKB resulted in abnormal division phenotypes or mitotic impairments. U0126, a specific mitogen-activated protein kinase kinase (MEK) inhibitor, caused significantly altered morphologies of early embryos together with a decrease in protein expression and kinase activity of AURKB. Our results indicated that the activity of AURKB was required for regulating multiple stages of mitotic progression in the early development of mouse zygotes and was correlated with the activation of the MAPK pathway.展开更多
基金Project supported by the National Natural Science Foundation of China(11071184)the National Natural Science Foundation of Shanxi Province of China(2012011015-6)
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.
基金supported by grants from the National Natural Science Foundation of China(814703628117190581272187)
文摘Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of erythropoiesis is that following each mitosis the daughter cells are morphologically and functionally different from the parent cell from which they are derived, demonstrating the need to study erythropoiesis in a stage-specific manner. This has been impossible until recently due to lack of methods for isolating erythroid cells at each distinct developmental stage. This review summarizes recent advances in the development of methods for isolating both murine and human erythroid cells and their applications. These methods provide powerful means for studying normal and impaired erythropoiesis associated with hematological disorders.
基金supported by the National Natural Science Foundation of China (Grant No. 81070527)
文摘Aurora kinases have become a hot topic for research as they have been found to play an important role in various stages of mitotic cell division and to participate in malignant conversions of tumors. The participation of Aurora kinases in the regulation of oocyte meiosis has been recently reported, but their participation in mammalian early embryonic development remained unclear. The object of our study was to establish the spatio-temporal expression pattern of Aurora kinase B (AURKB) in mouse zygotes during the first cleavage, to reveal its functions in the early development of mouse zygotes, and to define the involvement of AURKB in mitogen-activated protein kinase (MAPK) signaling. Our results showed that in mouse zygotes AURKB expression increased in G1 phase and peaked in M phase. AURKB protein distribution was found to be in association with nuclei and distributed throughout the cytoplasm in a cell cycle-dependent manner. Functional disruption of AURKB resulted in abnormal division phenotypes or mitotic impairments. U0126, a specific mitogen-activated protein kinase kinase (MEK) inhibitor, caused significantly altered morphologies of early embryos together with a decrease in protein expression and kinase activity of AURKB. Our results indicated that the activity of AURKB was required for regulating multiple stages of mitotic progression in the early development of mouse zygotes and was correlated with the activation of the MAPK pathway.
