Abstract
Recently, increasing evidence has shown that CDGSH iron sulfur domain 2 (CISD2) is involved in the initiation and metastasis of several cancers. However, the evidence of its potential role in pancreatic cancer is still lacking. In our present study, CISD2 was found to be increased in pancreatic cancer samples and multiple cell lines. Moreover, statistical analysis revealed that a high level of CISD2 was related to advanced clinical stage, advanced T-stage, positive vascular invasion, positive distant metastasis, and larger tumor size. In addition, multivariate analysis suggests that CISD2 was an independent prognostic factor in pancreatic cancer. Importantly, downregulation of CISD2 was capable of inhibiting the survival and growth of pancreatic cancer cells. Mechanistic study showed that inactivation of the Wnt/β-catenin pathway contributed to the CISD2 deficit-induced death of pancreatic cancer cells. Furthermore, we showed that CISD2 silencing significantly inhibited EMT via the Wnt/β-catenin pathway. Finally, in nude mice, the CISD2 deficit suppressed the tumorigenesis of pancreatic cancer cells. Collectively, our study demonstrated that CISD2 could be an independent prognostic factor for pancreatic cancer and suggested that the CISD2/Wnt/β-catenin pathway contributes to the proliferation of pancreatic cancer cells and EMT, hinting at a novel promising molecular target in the therapeutic strategy for pancreatic cancer.