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Current Molecular Medicine
ISSN (Print): 1566-5240
ISSN (Online): 1875-5666
VOLUME: 14
ISSUE: 3
DOI: 10.2174/1566524014666140228120913









Stathmin, Interacting with Nf-κB, Promotes Tumor Growth and Predicts Poor Prognosis of Pancreatic Cancer

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Author(s): Y. Lu, C. Liu, H. Cheng, Y. Xu, J. Jiang, J. Xu, J. Long, L. Liu and X. Yu
Pages 328-339 (12)
Abstract:
Stathmin (STMN) has been known as a p53-regulated protein and has been shown to play an oncogenic role in a range of human malignancies. Paradoxically, most recent studies demonstrated that stathmin has a dual function as both an oncogene and a metastasis suppressor. Stathmin is a member of microtubule dynamic destabilizing proteins and stathmin-regulated microtubule disruption could lead to a variety of cell dysfunctions such as enhanced chronic hypoxia in pancreatic cancer. In this study, we identified that stathmin promotes proliferation of pancreatic cancer cells by an underlying nuclear factor kappa B (Nf-κB) interacting mechanism. In human specimens, stathmin was significantly overexpressed in pancreatic cancer tissues and high expression of stathmin was correlated with vascular emboli (p=0.028), tumor size (p=0.019), and overall survival (p=0.031). Functional assays showed that knockdown of stathmin significantly reduced pancreatic cancer cell viability, colony formation, and arrested the cell cycle at the G2/M phase. Furthermore, silence of stathmin could reduce pancreatic tumor growth in nude mice. For the mechanism, Western blot analyses demonstrated that Nf-κB (p65) was significantly down-regulated when stathmin was silenced. In addition, co-immunoprecipitation (CoIP) assay suggested that stathmin was able to interact with Nf-κB (p65). Our findings indicate that stathmin might play its oncogenic role by an interaction with Nf-κB pathway, which may reveal a novel mechanism to uncover the role of microtubule-destabilizing stathmin in pancreatic cancer environment as well as provide a potential therapeutic strategy for pancreatic cancer.
Keywords:
Nf-κB, pancreatic cancer, prognosis, stathmin, tumor growth.
Affiliation:
No. 270, Dong'An Road, Xuhui District, Shanghai, 200032, P.R. China.