Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein

// Weiwei Sheng 1 , Ming Dong 1 , Chuanping Chen 2 , Yang Li 3 , Qingfeng Liu 4 , Qi Dong 4 1 Department of General Surgery, Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, 110001, China 2 Department of Clinical Laboratory, The Sixth Peoples’ Hospital of Shenyang City, 110003, China 3 Department of Cell Biology, China Medical University, Shenyang, 110001, China 4 Department of General Surgery, The Peoples’ Hospital of Liaoning Province, Shenyang, 110015, China Correspondence to: Ming Dong, e-mail: cmudongming@sohu.com Keywords: Musashi2, Numb, invasion and metastasis, pancreatic cancer Received: September 21, 2015     Accepted: March 11, 2016     Published: April 15, 2016 ABSTRACT Musashi2-Numb interaction plays a vital role in the progression of myeloid leukemia. However, its potential role in solid cancers has rarely been reported. We investigated the coordinate function of Musashi2-Numb in the development of pancreatic cancer (PC) in vitro and vivo . Both Musashi2 protein and mRNA levels were higher in PC tissues than that in paired normal pancreas ( P <0.05). Musashi2 overexpression and Numb positive expression were positively and negatively associated with tumor size and UICC stage, respectively ( P <0.05). Multivariate analysis identified Musashi2 and Numb as adverse and favorable independent indicators for the survival of PC patients. Moreover, patients with high Musashi2 expression combining with negative Numb expression had a significantly worse overall survival ( P =0.001). The negative relationship between Musashi2 and Numb was found at both PC tissue and cell levels. These two endogenous proteins can be co-immunoprecipitated from PC cell lines, and Musashi2 silence up-regulated Numb protein in vitro and vivo . Meanwhile, its silence decreased cell invasion and migration in vitro and inhibited the growth of subcutaneous tumors and the frequency of liver metastasis in vivo . However, Numb knockdown significantly reversed the decrease of cell invasion and migration induced by Musashi2 silence. Musashi2 promotes the development and progression of pancreatic cancer by down-regulating Numb protein. The interaction of Musashi2-Numb plays a significant role in the development and progression of PC.