Work

NudCL2 suppresses pancreatic cancer progression by inhibiting SLC7A11-mediated EMT and metastasis

Year: 2025

Type: article

Abstract: Pancreatic cancer (PC) is a highly aggressive malignancy with limited therapeutic options and poor prognosis. NudC-like protein 2 (NudCL2), a molecular cochaperone of HSP90, has been implicated in various cellular processes; however, its role in pancreatic cancer remains poorly understood. In this study, we report that NudCL2 expression is significantly downregulated in PC tissues and is correlated with poor patient survival. The results of functional assays revealed that NudCL2 knockdown enhances cell invasion and migration in vitro and promotes lung and liver metastases in vivo. Further analysis revealed solute carrier family 7 member 11 (SLC7A11) as a key downstream effector that was upregulated upon NudCL2 depletion. Suppression of SLC7A11 reversed the increase in cell motility induced by NudCL2 depletion. Mechanistically, our findings suggest that NudCL2 regulates the transcriptional activity of SLC7A11 and that the NudCL2/SLC7A11 axis may suppress cell motility by inhibiting the epithelial-mesenchymal transition (EMT) pathway. Collectively, these results highlight the important role of NudCL2 in PC progression through the modulation of EMT via SLC7A11, providing valuable insights into its potential as both a therapeutic target and a prognostic biomarker.

Source: Experimental Cell Research

DOI: 10.1016/j.yexcr.2025.114730