STMN2 overexpression promotes cell proliferation and EMT in pancreatic cancer mediated by WNT/β-catenin signaling

Abstract Background: STMN2, as a key regulator in microtubule disassembly and dynamics, has been recently reported to participate in cancer development. However, the corresponding role in pancreatic ductal adenocarcinoma (PC), to our knowledge has not been reported. Methods: We investigate the potential role of STMN2 in the development of PC in vitro and vivo. Results: Overexpression of STMN2 was prevalently observed in human PC tissues compared with that in paired pancreas (44/81,54.3% vs 15/81, 18.5%, P<0.01), which was positively with multiple advanced stage of PC patients (tumor size, T stage, lymph-node metastasis and the poor survival). Meanwhile, a close correlation between high STMN2 and cytoplasmic/nuclear β-catenin expression (P=0.007) was observed in PC tissues and cell lines. STMN2 overexpression induced EMT and cell proliferation in vitro, which stimulated EMT-like cellular morphology, cell motility and proliferation, and the change of EMT (Snail1, E-cad and Vimentin) and Cyclin D1 signaling. However, XAV939 inhibited STMN2 overexpression-enhanced EMT and proliferation. Conversely, KY19382 reversed STMN2 silencing- inhibited EMT and cell proliferation in vitro. In addition, STMN2 promoted subcutaneous tumor growth with the overexpression of EMT and Cyclin D1 signaling. Finally, activated STMN2 and β-catenin were co-localized in cytoplasm/nuclear in vitro. Conclusions: β-catenin/TCF-mediated the transcription of STMN2. STMN2 overexpression promotes aggressive clinical stage of PC patients and promotes EMT and cell proliferation in vitro and vivo mediated by WNT/β-catenin signaling.