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.