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Dysbindin promotes progression of pancreatic ductal adenocarcinoma via direct activation of PI3K Free
Cheng Fang1 † Xin Guo1† Xing Lv1† Ruozhe Yin1 Xiaohui Lv2 Fengsong Wang3 Jun Zhao4 Quan Bai5 Xuebiao Yao6,* Yong Chen1,*
1 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China

2 Department of Gynecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi’an, China

3 Department of Biology, School of Life Science, Anhui Medical University, Hefei, China

4 Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, China

5 Institute of Modern Separation Science, College of Chemistry & Materials Science, Northwest University, Xi’an, China

6 Department of Hefei Laboratory for Physical Sciences at Microscale, School of Life Science, University of Science and Technology of China, Hefei, China

†These authors contributed equally to this work. *Correspondence to:Yong Chen, E-mail:; Xuebiao Yao, E-mail:
J Mol Cell Biol, Volume 9, Issue 6, December 2017, Pages 504-515
Keyword: pancreatic ductal adenocarcinoma, dysbindin, cell cycle, PI3K, prognostic factor

Pancreatic ductal adenocarcinoma (PDAC) represents a biggest challenge in clinic oncology due to its invasiveness and lack of targeted 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 promotes tumor growth both in vitro and in vivo by accelerating the G1/S phase transition in cell cycle via PI3K/AKT signaling pathway. 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 independent prognostic factor for pancreatic ductal adenocarcinoma (P = 0.001). Thus, our findings reveal that dysbindin is a novel PI3K activator and promotes PDAC progression via stimulation of PI3K/AKT. Dysbindin therefore represents a potential target for prognosis and therapy of PDAC.